Is EAF2 p.Gly78Val (c.233G>T) pathogenic?

EAF2 p.Gly78Val (c.233G>T) is classified Uncertain significance in EAF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-04). AlphaMissense: likely pathogenic (0.9928); Very rare (popmax 0.000343%, nfe).

How common is EAF2 p.Gly78Val (c.233G>T) in the general population?

EAF2 p.Gly78Val (c.233G>T) is very rare (popmax 0.000343%, nfe) (gnomAD).

What do computational predictors say about EAF2 p.Gly78Val (c.233G>T)?

AlphaMissense predicts likely pathogenic (score 0.9928) — an in-silico prediction, not a clinical call.

EAF2 p.Gly78Val

c.233G>T · VCV3843217

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9928 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000343%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9928	likely pathogenic
REVEL	0.785	moderately pathogenic-leaning
SaProt	LLR -17.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	29.9	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

Grpmax group 0.000343% European (non-Finnish) · 4/1,164,516 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000284% 4/1,407,076 alleles · very 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: EAF2
Protein: p.Gly78Val
Coding: c.233G>T
MANE Select: NM_019100 · reported on NM_018456
Type: single nucleotide variant
Location: chr3:121854718 (GRCh38)
Structure: AlphaFold pLDDT 75.46 · 18 PDB

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-gly78val (accessed [today's date]).

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