Is EFNA2 p.Ile71Phe (c.211A>T) pathogenic?

EFNA2 p.Ile71Phe (c.211A>T) is classified Uncertain significance in EFNA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely pathogenic (0.9855); Absent from gnomAD v4.1.

How common is EFNA2 p.Ile71Phe (c.211A>T) in the general population?

EFNA2 p.Ile71Phe (c.211A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFNA2 p.Ile71Phe (c.211A>T)?

AlphaMissense predicts likely pathogenic (score 0.9855) — an in-silico prediction, not a clinical call.

EFNA2 p.Ile71Phe

c.211A>T · VCV4663308

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9855 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9855	likely pathogenic
REVEL	0.491	indeterminate
SaProt	LLR -13.74	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 0.97, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 14 kb · p 0.68 · regional, not allelic
Overall
CADD	26.5	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

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: EFNA2
Protein: p.Ile71Phe
Coding: c.211A>T
MANE Select: NM_001405
Type: single nucleotide variant
Location: chr19:1295615 (GRCh38)
Gene constraint: LOEUF 1.447 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 1 PDB
Residue 71: a β-strand; the ephrin rbd domain

Full EFNA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFNA2 p.Ala180Thr Uncertain significance ★ ⚠ same type
EFNA2 p.Arg105His Uncertain significance ★ ⚠ same type
EFNA2 p.Arg161Gln Uncertain significance ★ ⚠ same type
EFNA2 p.Arg171Trp Uncertain significance ★ same type
EFNA2 p.Arg43Leu Uncertain significance ★ same type
EFNA2 p.Arg6Pro Uncertain significance ★ ⚠ same type
EFNA2 p.Asn157Ser Uncertain significance ★ ⚠ same type
EFNA2 p.Asn33Thr 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/efna2-p-ile71phe (accessed [today's date]).

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