Is EAF2 p.Arg99Gln (c.296G>A) pathogenic?

EAF2 p.Arg99Gln (c.296G>A) is classified Uncertain significance in EAF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). AlphaMissense: likely benign (0.0962); Very rare (popmax 0.00369%, sas).

How common is EAF2 p.Arg99Gln (c.296G>A) in the general population?

EAF2 p.Arg99Gln (c.296G>A) is very rare (popmax 0.00369%, sas) (gnomAD).

What do computational predictors say about EAF2 p.Arg99Gln (c.296G>A)?

AlphaMissense predicts likely benign (score 0.0962) — an in-silico prediction, not a clinical call.

EAF2 p.Arg99Gln

c.296G>A · VCV3506336

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0962 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00369%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0962	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -10.85	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP -0.93, phastCons 1
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00369% South Asian · 3/81,382 alleles

Filtering AF 0.00158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00219% 31/1,418,454 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00369%	27,127
European (non-Finnish)	0.00231%	43,266
Admixed American	0.00212%	47,160

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.Arg99Gln
Coding: c.296G>A
MANE Select: NM_019100 · reported on NM_018456
Type: single nucleotide variant
Location: chr3:121854781 (GRCh38)
Structure: AlphaFold pLDDT 75.46 · 18 PDB
Residue 99: a β-strand

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-arg99gln (accessed [today's date]).

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