AFG2B

Chr 15

AAA ATPase AFG2B

Also known as: DFNB119, NEDHLS, SPATA5L1

NCBI Gene: 79029 ENSG00000171763 UniProt: Q9BVQ7

This protein functions as an ATP-dependent chaperone essential for ribosomal large subunit biogenesis and maintains replication fork progression and genome stability as part of a chromatin-associated ATPase complex. Mutations cause autosomal recessive nonsyndromic deafness and a neurodevelopmental disorder with hearing loss and spasticity. The gene shows minimal constraint against loss-of-function variants (pLI near zero), consistent with its autosomal recessive inheritance pattern.

ResearchSummary from RefSeq, OMIM, UniProt

Enables identical protein binding activity and preribosome binding activity. Involved in ribosomal large subunit biogenesis. Located in cytoplasm and spindle. Implicated in autosomal recessive nonsyndromic deafness. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.07

Clinical Summary— AFG2B

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Gene-Disease Validity (ClinGen)

hearing loss, autosomal recessive 119 · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

22 unique Pathogenic / Likely Pathogenic· 120 VUS of 177 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.07LOEUF

pLI 0.000

Z-score 1.28

OE 0.74 (0.52–1.07)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.86Z-score

OE missense 0.88 (0.80–0.96)

346 obs / 394.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.52–1.07)

0≤0.351.4

Missense OE?0.88 (0.80–0.96)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 20 / 27.2Missense obs/exp: 346 / 394.1Syn Z: 0.48

ClinVar Variant Classifications

177 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic16

VUS120

Likely Benign14

Benign8

Conflicting3

Pathogenic

Likely Pathogenic

120

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	6	0	0	0	6
Likely Pathogenic	3	13	0	0	16
VUS	0	120	0	0	120
Likely Benign	0	5	0	9	14
Benign	0	4	1	3	8
Conflicting	—				3
Total	9	142	1	12	167

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

11 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap AFG2B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →