Is EAF1 p.Arg233Thr (c.698G>C) pathogenic?

EAF1 p.Arg233Thr (c.698G>C) is classified Uncertain significance in EAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-26). AlphaMissense: likely benign (0.1891); Very rare (popmax 8.58e-05%, nfe).

How common is EAF1 p.Arg233Thr (c.698G>C) in the general population?

EAF1 p.Arg233Thr (c.698G>C) is very rare (popmax 8.58e-05%, nfe) (gnomAD).

What do computational predictors say about EAF1 p.Arg233Thr (c.698G>C)?

AlphaMissense predicts likely benign (score 0.1891) — an in-silico prediction, not a clinical call.

EAF1 p.Arg233Thr

c.698G>C · VCV3274324

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1891 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.58e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1891	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -6.61	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 5.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 11 kb · p 3.8e-05 · regional, not allelic
Overall
CADD	23.9	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 8.58e-05% European (non-Finnish) · 1/1,166,000 alleles

Overall 0.000657% 1/152,140 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: EAF1
Protein: p.Arg233Thr
Coding: c.698G>C
MANE Select: NM_033083
Type: single nucleotide variant
Location: chr3:15436513 (GRCh38)
Gene constraint: LOEUF 1.012 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.79 · 2 PDB
Residue 233: the 'disordered' region; the 'necessary for transactivation activity' region

Full EAF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EAF1 p.Arg233Met Uncertain significance ★ ⚠ same residue
EAF1 p.Asp206= Benign ★★ same type
EAF1 p.Thr133= Benign ★★ same type
EAF1 p.Ala147Ser Uncertain significance ★ ⚠ same type
EAF1 p.Arg122Gln Uncertain significance ★ ⚠ same type
EAF1 p.Arg27Gln Uncertain significance ★ ⚠ same type
EAF1 p.Asn216Ser Uncertain significance ★ ⚠ same type
EAF1 p.Asn6Ser 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/eaf1-p-arg233thr (accessed [today's date]).

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