Is EAF2 p.Phe31Cys (c.92T>G) pathogenic?

EAF2 p.Phe31Cys (c.92T>G) is classified Uncertain significance in EAF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely pathogenic (0.9789); Absent from gnomAD v4.1.

How common is EAF2 p.Phe31Cys (c.92T>G) in the general population?

EAF2 p.Phe31Cys (c.92T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EAF2 p.Phe31Cys (c.92T>G)?

AlphaMissense predicts likely pathogenic (score 0.9789) — an in-silico prediction, not a clinical call.

EAF2 p.Phe31Cys

c.92T>G · rs1164975328 · VCV3086806

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9789 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9789	likely pathogenic
REVEL	0.472	indeterminate
SaProt	LLR -11.09	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.1, phastCons 1
Overall
CADD	32.0	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: EAF2
Protein: p.Phe31Cys
Coding: c.92T>G
MANE Select: NM_019100 · reported on NM_018456
dbSNP: rs1164975328
Type: single nucleotide variant
Location: chr3:121835377 (GRCh38)
Structure: AlphaFold pLDDT 75.46 · 18 PDB
Residue 31: the 'disordered' region

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-phe31cys (accessed [today's date]).

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