Is EFNA3 p.Ser69Ala (c.205T>G) pathogenic?

EFNA3 p.Ser69Ala (c.205T>G) is classified Uncertain significance in EFNA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-20). AlphaMissense: likely benign (0.1276); Absent from gnomAD v4.1.

How common is EFNA3 p.Ser69Ala (c.205T>G) in the general population?

EFNA3 p.Ser69Ala (c.205T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFNA3 p.Ser69Ala (c.205T>G)?

AlphaMissense predicts likely benign (score 0.1276) — an in-silico prediction, not a clinical call.

EFNA3 p.Ser69Ala

c.205T>G · rs2526499765 · VCV2268066

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1276 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1276	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -6.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,598 bp · p 0.15 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EFNA3
Protein: p.Ser69Ala
Coding: c.205T>G
MANE Select: NM_004952
dbSNP: rs2526499765
Type: single nucleotide variant
Location: chr1:155085167 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.84
Residue 69: the ephrin rbd domain; a disulfide bond

Full EFNA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFNA3 p.Ser133= Benign ★★ same type
EFNA3 p.Ala101Ser Uncertain significance ★ ⚠ same type
EFNA3 p.Ala168Val Uncertain significance ★ ⚠ same type
EFNA3 p.Arg219Gln Uncertain significance ★ ⚠ same type
EFNA3 p.Arg219Trp Uncertain significance ★ ⚠ same type
EFNA3 p.Arg45Trp Uncertain significance ★ ⚠ same type
EFNA3 p.Asn193Asp Uncertain significance ★ ⚠ same type
EFNA3 p.Asp57Glu 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/efna3-p-ser69ala (accessed [today's date]).

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