Is EPHA6 p.Ser402Phe (c.1205C>T) pathogenic?

EPHA6 p.Ser402Phe (c.1205C>T) is classified Uncertain significance in EPHA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). Ultra-rare (popmax 0.0198%, sas).

How common is EPHA6 p.Ser402Phe (c.1205C>T) in the general population?

EPHA6 p.Ser402Phe (c.1205C>T) is ultra-rare (popmax 0.0198%, sas) (gnomAD).

EPHA6 p.Ser402Phe

c.1205C>T · rs752883948 · VCV3089598

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.096	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 853 kb · p 0.00012 · regional, not allelic
Overall
CADD	19.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0198% South Asian · 18/91,070 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00112% 18/1,613,660 alleles · ultra-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: EPHA6
Protein: p.Ser402Phe
Coding: c.1205C>T
MANE Select: NM_001080448
dbSNP: rs752883948
Type: single nucleotide variant
Location: chr3:97226354 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.90
Residue 402: the fibronectin type-iii 1 domain

Full EPHA6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPHA6 p.Ala805Val Benign ★★ same type
EPHA6 p.Thr72= Benign ★★ same type
EPHA6 p.Ala116Val Uncertain significance ★ same type
EPHA6 p.Ala14Thr Uncertain significance ★ same type
EPHA6 p.Ala190Val Uncertain significance ★ same type
EPHA6 p.Ala382Pro Uncertain significance ★ same type
EPHA6 p.Ala614Val Uncertain significance ★ same type
EPHA6 p.Ala636Thr 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/epha6-p-ser402phe (accessed [today's date]).

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