Is ESPN p.Ala296Val (c.887C>T) pathogenic?

ESPN p.Ala296Val (c.887C>T) is classified Likely benign in ESPN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-22). AlphaMissense: likely benign (0.1124); Rare (popmax 0.276%, afr).

How common is ESPN p.Ala296Val (c.887C>T) in the general population?

ESPN p.Ala296Val (c.887C>T) is rare (popmax 0.276%, afr) (gnomAD).

What do computational predictors say about ESPN p.Ala296Val (c.887C>T)?

AlphaMissense predicts likely benign (score 0.1124) — an in-silico prediction, not a clinical call.

ESPN p.Ala296Val

c.887C>T · rs146588006 · VCV721600

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1124 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.276%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1124	likely benign
REVEL	0.228	benign-leaning
SaProt	LLR -6.94	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 3.9	GERP -2.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 21 kb · p 0.002 · regional, not allelic
Overall
CADD	20.5	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 0.276% African / African-American · 206/74,750 alleles

Filtering AF 0.245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.233%

Overall 0.0139% 222/1,598,038 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.276%	363
Admixed American	0.0138%	7,269
Remaining individualsnot grpmax-eligible	0.0113%	8,825
European (non-Finnish)	8.52e-05%	1,173,573

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: ESPN
Protein: p.Ala296Val
Coding: c.887C>T
MANE Select: NM_031475
dbSNP: rs146588006
Type: single nucleotide variant
Location: chr1:6440962 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.76

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

Similar variants

ESPN c.1464+1G>A Likely pathogenic ★★ same type
ESPN p.Ala139Thr Uncertain significance ★★ ⚠ same type
ESPN p.Ala23Thr Uncertain significance ★★ ⚠ same type
ESPN p.Ala484Thr Uncertain significance ★★ ⚠ same type
ESPN p.Ala591Val Uncertain significance ★★ ⚠ same type
ESPN p.Ala610Pro Uncertain significance ★★ ⚠ same type
ESPN p.Ala624Thr Uncertain significance ★★ ⚠ same type
ESPN p.Ala729Glu 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/espn-p-ala296val (accessed [today's date]).

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