FAM171B

Chr 2

family with sequence similarity 171 member B

Also known as: KIAA1946

NCBI Gene: 165215 ENSG00000144369 UniProt: Q6P995 OMIM: 620309

The FAM171B protein is predicted to localize to cellular membranes and function at synapses. Mutations cause autosomal recessive intellectual disability with seizures and spasticity, typically presenting in early childhood. This gene shows significant constraint against loss-of-function variants (LOEUF 0.408), suggesting intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq

Predicted to be located in membrane. Predicted to be active in synapse. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.41

Clinical Summary— FAM171B

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.

📋

ClinVar Variants

84 VUS of 101 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.485

Z-score 4.12

OE 0.22 (0.12–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.51Z-score

OE missense 0.80 (0.73–0.87)

344 obs / 432.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.12–0.41)

0≤0.351.4

Missense OE?0.80 (0.73–0.87)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 7 / 32.3Missense obs/exp: 344 / 432.1Syn Z: 0.40

ClinVar Variant Classifications

101 submitted variants in ClinVar

ClinVar

Classification Summary

VUS84

Likely Benign4

Benign6

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	84	0	84
Likely Benign	4	0	4
Benign	2	4	6
Total	90	4	94

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap FAM171B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →