Is EOLA2 p.Phe8Ser (c.23T>C) pathogenic?

EOLA2 p.Phe8Ser (c.23T>C) is classified Uncertain significance in EOLA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-15). AlphaMissense: likely pathogenic (0.7246); Rare (popmax 0.121%, amr).

How common is EOLA2 p.Phe8Ser (c.23T>C) in the general population?

EOLA2 p.Phe8Ser (c.23T>C) is rare (popmax 0.121%, amr) (gnomAD).

What do computational predictors say about EOLA2 p.Phe8Ser (c.23T>C)?

AlphaMissense predicts likely pathogenic (score 0.7246) — an in-silico prediction, not a clinical call.

EOLA2 p.Phe8Ser

c.23T>C · rs782444250 · VCV3089264

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7246 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.121%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7246	likely pathogenic · top 4% in EOLA2
REVEL	0.766	pathogenic-leaning
SaProt	LLR -14.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.5	GERP 1.5, phastCons 0.94
Regional constraint	o/e 0.86	unconstrained · MANE · 1,327 bp · p 0.12 · regional, not allelic
Overall
CADD	23.8	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 0.121% Admixed American · 55/45,603 alleles

Filtering AF 0.0951% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.086%

Overall 0.00483% 58/1,200,752 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.121%	829
Remaining individualsnot grpmax-eligible	0.00635%	15,742

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: EOLA2
Protein: p.Phe8Ser
Coding: c.23T>C
MANE Select: NM_001013845
dbSNP: rs782444250
Type: single nucleotide variant
Location: chrX:149933852 (GRCh38)
Structure: AlphaFold pLDDT 95.36
Residue 8: the asch domain

Full EOLA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EOLA2 p.Arg28Cys Conflicting classifications of pathogenicity ★ ⚠ same type
EOLA2 p.Glu132= Likely benign ★ same type
EOLA2 p.Pro133= Likely benign ★ same type
EOLA2 p.Val105= Likely benign ★ same type
HSFX4 p.Asn102= Likely benign ★ same type
HSFX4 p.Tyr313= Likely benign ★ 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/eola2-p-phe8ser (accessed [today's date]).

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