Is EPB41L2 p.Ser302Phe (c.905C>T) pathogenic?

EPB41L2 p.Ser302Phe (c.905C>T) is classified Uncertain significance in EPB41L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: ambiguous (0.4932); Very rare (popmax 0.00264%, nfe).

How common is EPB41L2 p.Ser302Phe (c.905C>T) in the general population?

EPB41L2 p.Ser302Phe (c.905C>T) is very rare (popmax 0.00264%, nfe) (gnomAD).

What do computational predictors say about EPB41L2 p.Ser302Phe (c.905C>T)?

AlphaMissense predicts ambiguous (score 0.4932) — an in-silico prediction, not a clinical call.

EPB41L2 p.Ser302Phe

c.905C>T · rs781423429 · VCV2318764

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4932 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00264%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4932	ambiguous
REVEL	0.563	indeterminate
SaProt	LLR -12.06	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 98 kb · p 0.029 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00264% European (non-Finnish) · 31/1,173,962 alleles

Filtering AF 0.00189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00165%

Overall 0.00193% 31/1,605,160 alleles · very rare

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: EPB41L2
Protein: p.Ser302Phe
Coding: c.905C>T
MANE Select: NM_001431
dbSNP: rs781423429
Type: single nucleotide variant
Location: chr6:130904489 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.76 (gnomAD)
Structure: AlphaFold pLDDT 60.14
Residue 302: the ferm domain

Full EPB41L2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPB41L2 c.2044-243G>T Uncertain significance ★ same type
EPB41L2 p.Ala322Ser Uncertain significance ★ ⚠ same type
EPB41L2 p.Ala322Val Uncertain significance ★ ⚠ same type
EPB41L2 p.Ala481Thr Uncertain significance ★ ⚠ same type
EPB41L2 p.Ala52Val Uncertain significance ★ ⚠ same type
EPB41L2 p.Ala570Thr Uncertain significance ★ ⚠ same type
EPB41L2 p.Ala576Thr Uncertain significance ★ ⚠ same type
EPB41L2 p.Ala696Glu Uncertain significance ★ ⚠ 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/epb41l2-p-ser302phe (accessed [today's date]).

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