Is EAF2 p.Val53Ile (c.157G>A) pathogenic?

EAF2 p.Val53Ile (c.157G>A) is classified Uncertain significance in EAF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely benign (0.1166); Ultra-rare (popmax 0.0165%, mid).

How common is EAF2 p.Val53Ile (c.157G>A) in the general population?

EAF2 p.Val53Ile (c.157G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about EAF2 p.Val53Ile (c.157G>A)?

AlphaMissense predicts likely benign (score 0.1166) — an in-silico prediction, not a clinical call.

EAF2 p.Val53Ile

c.157G>A · VCV3506337

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1166 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1166	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -6.92	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 8.4	GERP 1.9, phastCons 1
Overall
CADD	24.8	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

Grpmax group 0.0165% Middle Eastern · 1/6,068 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.0013% 21/1,611,124 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,068
Ashkenazi Jewishnot grpmax-eligible	0.00677%	14,766
Remaining individualsnot grpmax-eligible	0.00321%	31,165
East Asian	0.00225%	44,522
Admixed American	0.00168%	59,518
African / African-American	0.00134%	74,778
South Asian	0.0011%	90,702
European (non-Finnish)	0.00102%	98,233

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: EAF2
Protein: p.Val53Ile
Coding: c.157G>A
MANE Select: NM_019100 · reported on NM_018456
Type: single nucleotide variant
Location: chr3:121844503 (GRCh38)
Structure: AlphaFold pLDDT 75.46 · 18 PDB
Residue 53: a turn

Full EAF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMAP1 p.Arg224Ter Uncertain significance ★★ same type
DMAP1 p.Arg283His Uncertain significance ★★ ⚠ same type
DMAP1 p.Tyr196Ser Uncertain significance ★★ ⚠ same type
DMAP1 p.Arg226Trp Likely pathogenic ★ same type
DMAP1 c.1344+3A>G Uncertain significance ★ same type
DMAP1 c.394-1G>C Uncertain significance ★ same type
DMAP1 p.Ala207Thr Uncertain significance ★ ⚠ same type
DMAP1 p.Ala2Thr 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/eaf2-p-val53ile (accessed [today's date]).

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