Is EAF2 p.Glu160Lys (c.478G>A) pathogenic?

EAF2 p.Glu160Lys (c.478G>A) is classified Uncertain significance in EAF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-23). AlphaMissense: likely benign (0.2329); Ultra-rare (popmax 0.0663%, mid).

How common is EAF2 p.Glu160Lys (c.478G>A) in the general population?

EAF2 p.Glu160Lys (c.478G>A) is ultra-rare (popmax 0.0663%, mid) (gnomAD).

What do computational predictors say about EAF2 p.Glu160Lys (c.478G>A)?

AlphaMissense predicts likely benign (score 0.2329) — an in-silico prediction, not a clinical call.

EAF2 p.Glu160Lys

c.478G>A · rs138459007 · VCV2588236

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2329 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0663%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2329	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -7.75	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 12	GERP 0.2, phastCons 1
Overall
CADD	23.4	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 0.0663% Middle Eastern · 4/6,036 alleles

Filtering AF 0.0226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00398% 64/1,608,252 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0663%	1,509
African / African-American	0.0107%	9,329
Remaining individualsnot grpmax-eligible	0.00964%	10,376
East Asian	0.0067%	14,935
Admixed American	0.00512%	19,517
South Asian	0.00445%	22,468
European (non-Finnish)	0.00306%	32,720

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.Glu160Lys
Coding: c.478G>A
MANE Select: NM_019100 · reported on NM_018456
dbSNP: rs138459007
Type: single nucleotide variant
Location: chr3:121857150 (GRCh38)
Structure: AlphaFold pLDDT 75.46 · 18 PDB
Residue 160: the sant domain; an α-helix

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-glu160lys (accessed [today's date]).

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