Is EPB41 p.Arg310Gln (c.929G>A) pathogenic?

EPB41 p.Arg310Gln (c.929G>A) is classified Uncertain significance in EPB41 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-22). AlphaMissense: likely pathogenic (0.6635); Ultra-rare (popmax 0.0165%, sas).

How common is EPB41 p.Arg310Gln (c.929G>A) in the general population?

EPB41 p.Arg310Gln (c.929G>A) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

What do computational predictors say about EPB41 p.Arg310Gln (c.929G>A)?

AlphaMissense predicts likely pathogenic (score 0.6635) — an in-silico prediction, not a clinical call.

EPB41 p.Arg310Gln

c.929G>A · rs577850620 · VCV2975805

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6635 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6635	likely pathogenic
REVEL	0.745	pathogenic-leaning
SaProt	LLR -10.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 31 kb · p 0.042 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% South Asian · 15/91,042 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00136% 22/1,613,402 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,069
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000509%	196,655

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EPB41
Protein: p.Arg310Gln
Coding: c.929G>A
MANE Select: NM_001376013
dbSNP: rs577850620
Type: single nucleotide variant
Location: chr1:29018247 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.72 · 3 PDB
Residue 310: the ferm domain; an α-helix

Full EPB41 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPB41 p.Arg310Trp Uncertain significance ★ ⚠ same residue
EPB41 p.Arg471Ter Pathogenic/Likely pathogenic ★★ same type
EPB41 p.Arg508Ter Pathogenic/Likely pathogenic ★★ same type
EPB41 p.Arg554Ter Pathogenic/Likely pathogenic ★★ same type
EPB41 p.Arg715Ter Pathogenic ★★ same type
EPB41 p.Gln274Ter Pathogenic ★★ same type
EPB41 p.Met210Val Pathogenic/Likely pathogenic ★★ ⚠ same type
EPB41 p.Tyr331Ter Pathogenic/Likely pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/epb41-p-arg310gln (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown