Is ENTREP3 p.Asp203Ala (c.608A>C) pathogenic?

ENTREP3 p.Asp203Ala (c.608A>C) is classified Uncertain significance in ENTREP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely pathogenic (0.697); Very rare (popmax 0.00492%, nfe).

How common is ENTREP3 p.Asp203Ala (c.608A>C) in the general population?

ENTREP3 p.Asp203Ala (c.608A>C) is very rare (popmax 0.00492%, nfe) (gnomAD).

What do computational predictors say about ENTREP3 p.Asp203Ala (c.608A>C)?

AlphaMissense predicts likely pathogenic (score 0.697) — an in-silico prediction, not a clinical call.

ENTREP3 p.Asp203Ala

c.608A>C · rs375507400 · VCV2542162

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.697 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00492%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.697	likely pathogenic
REVEL	0.332	indeterminate
SaProt	LLR -8.26	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 6.1	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,092 bp · p 0.33 · regional, not allelic
Overall
CADD	26.4	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 0.00492% European (non-Finnish) · 58/1,179,232 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00391% 63/1,612,836 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00492%	20,332
Remaining individualsnot grpmax-eligible	0.00481%	20,809
Admixed American	0.00167%	59,928
African / African-American	0.00134%	74,848

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: ENTREP3
Protein: p.Asp203Ala
Coding: c.608A>C
MANE Select: NM_006589
dbSNP: rs375507400
Type: single nucleotide variant
Location: chr1:155253638 (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-asp203ala (accessed [today's date]).

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