Is ENTREP3 p.Tyr255His (c.763T>C) pathogenic?

ENTREP3 p.Tyr255His (c.763T>C) is classified Uncertain significance in ENTREP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). AlphaMissense: likely pathogenic (0.9987); Absent from gnomAD v4.1.

How common is ENTREP3 p.Tyr255His (c.763T>C) in the general population?

ENTREP3 p.Tyr255His (c.763T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ENTREP3 p.Tyr255His (c.763T>C)?

AlphaMissense predicts likely pathogenic (score 0.9987) — an in-silico prediction, not a clinical call.

ENTREP3 p.Tyr255His

c.763T>C · VCV4018304

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9987	likely pathogenic · top 1% in ENTREP3
REVEL	0.366	indeterminate
SaProt	LLR -7.60	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,092 bp · p 0.33 · regional, not allelic
Overall
CADD	28.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ENTREP3
Protein: p.Tyr255His
Coding: c.763T>C
MANE Select: NM_006589
Type: single nucleotide variant
Location: chr1:155251764 (GRCh38)
Structure: AlphaFold pLDDT 53.93

Full ENTREP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENTREP3 p.Ala229Thr Uncertain significance ★ ⚠ same type
ENTREP3 p.Ala452Thr Uncertain significance ★ ⚠ same type
ENTREP3 p.Arg212Gln Uncertain significance ★ ⚠ same type
ENTREP3 p.Arg212Trp Uncertain significance ★ ⚠ same type
ENTREP3 p.Arg25His Uncertain significance ★ ⚠ same type
ENTREP3 p.Arg371Pro Uncertain significance ★ ⚠ same type
ENTREP3 p.Arg393Gln Uncertain significance ★ ⚠ same type
ENTREP3 p.Arg400Cys 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/entrep3-p-tyr255his (accessed [today's date]).

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