Is EPS8 p.Ala150Val (c.449C>T) pathogenic?

EPS8 p.Ala150Val (c.449C>T) is classified Uncertain significance in EPS8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-10). AlphaMissense: likely benign (0.1901); Ultra-rare (popmax 0.03%, amr); Associated with Inborn genetic diseases.

What condition is associated with EPS8 p.Ala150Val (c.449C>T)?

EPS8 p.Ala150Val (c.449C>T) is associated with Inborn genetic diseases, autosomal recessive nonsyndromic hearing loss 102 (ClinVar).

How common is EPS8 p.Ala150Val (c.449C>T) in the general population?

EPS8 p.Ala150Val (c.449C>T) is ultra-rare (popmax 0.03%, amr) (gnomAD).

What do computational predictors say about EPS8 p.Ala150Val (c.449C>T)?

AlphaMissense predicts likely benign (score 0.1901) — an in-silico prediction, not a clinical call.

EPS8 p.Ala150Val

c.449C>T · rs769820275 · VCV1301461

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1901 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1901	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -10.65	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 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 62 kb · p 0.26 · regional, not allelic
Overall
CADD	23.5	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 0.03% Admixed American · 18/59,998 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00124% 20/1,613,910 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,333
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	8.48e-05%	1,179,912

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: EPS8
Protein: p.Ala150Val
Coding: c.449C>T
MANE Select: NM_004447
dbSNP: rs769820275
Type: single nucleotide variant
Location: chr12:15669454 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.77 · 2 PDB
Residue 150: the ptb domain

Full EPS8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive nonsyndromic hearing loss 102

Similar variants

EPS8 c.205-8A>G Uncertain significance ★★ same condition
EPS8 p.Ala416Asp Uncertain significance ★★ ⚠ same condition
EPS8 p.Arg195Trp Uncertain significance ★★ ⚠ same condition
EPS8 p.Arg403Trp Uncertain significance ★★ ⚠ same condition
EPS8 p.Arg432Gln Uncertain significance ★★ ⚠ same condition
EPS8 p.Arg434Cys Uncertain significance ★★ ⚠ same condition
EPS8 p.Arg597Cys Uncertain significance ★★ ⚠ same condition
EPS8 p.Arg597Ser Uncertain significance ★★ ⚠ same condition

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/eps8-p-ala150val (accessed [today's date]).

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