FAM124A

Chr 13

family with sequence similarity 124 member A

This gene encodes a protein that functions in cellular stress response and protein quality control pathways. Mutations cause autosomal recessive developmental and epileptic encephalopathy with severe intellectual disability, seizures, and movement disorders typically presenting in infancy. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

LOEUF 1.43
Clinical SummaryFAM124A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
59 unique Pathogenic / Likely Pathogenic· 95 VUS of 168 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.43LOEUF
pLI 0.000
Z-score 0.25
OE 0.93 (0.621.43)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.99Z-score
OE missense 0.85 (0.770.94)
292 obs / 343.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.93 (0.621.43)
00.351.4
Missense OE0.85 (0.770.94)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 15 / 16.1Missense obs/exp: 292 / 343.8Syn Z: 1.30

ClinVar Variant Classifications

168 submitted variants in ClinVar

Classification Summary

Pathogenic57
Likely Pathogenic2
VUS95
Likely Benign5
Benign4
57
Pathogenic
2
Likely Pathogenic
95
VUS
5
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
57
0
57
Likely Pathogenic
0
0
2
0
2
VUS
0
88
7
0
95
Likely Benign
0
4
1
0
5
Benign
0
1
1
2
4
Total093682163

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

View in ClinVar →

Protein Context — Lollipop Plot

FAM124A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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