Is EAF1 p.Ser198Phe (c.593C>T) pathogenic?

EAF1 p.Ser198Phe (c.593C>T) is classified Uncertain significance in EAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). AlphaMissense: ambiguous (0.379); Ultra-rare (popmax 0.0967%, amr).

How common is EAF1 p.Ser198Phe (c.593C>T) in the general population?

EAF1 p.Ser198Phe (c.593C>T) is ultra-rare (popmax 0.0967%, amr) (gnomAD).

What do computational predictors say about EAF1 p.Ser198Phe (c.593C>T)?

AlphaMissense predicts ambiguous (score 0.379) — an in-silico prediction, not a clinical call.

EAF1 p.Ser198Phe

c.593C>T · rs754503030 · VCV2277670

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.379 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0967%, amr)

Computational evidence

Protein change
AlphaMissense	0.379	ambiguous
REVEL	0.377	indeterminate
SaProt	LLR -13.46	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 11 kb · p 3.8e-05 · regional, not allelic
Overall
CADD	31.0	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 0.0967% Admixed American · 58/59,998 alleles

Filtering AF 0.0767% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0696%

Overall 0.00366% 59/1,613,898 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0967%	1,034
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Ser198Phe
Coding: c.593C>T
MANE Select: NM_033083
dbSNP: rs754503030
Type: single nucleotide variant
Location: chr3:15436408 (GRCh38)
Gene constraint: LOEUF 1.012 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.79 · 2 PDB
Residue 198: 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.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.Arg233Met Uncertain significance ★ ⚠ same type
EAF1 p.Arg233Thr Uncertain significance ★ ⚠ same type
EAF1 p.Arg27Gln Uncertain significance ★ ⚠ same type
EAF1 p.Asn216Ser 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-ser198phe (accessed [today's date]).

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