Is ENTREP2 p.Val190Met (c.568G>A) pathogenic?

ENTREP2 p.Val190Met (c.568G>A) is classified Uncertain significance in ENTREP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). AlphaMissense: likely pathogenic (0.8055); Ultra-rare (popmax 0.0687%, nfe).

How common is ENTREP2 p.Val190Met (c.568G>A) in the general population?

ENTREP2 p.Val190Met (c.568G>A) is ultra-rare (popmax 0.0687%, nfe) (gnomAD).

What do computational predictors say about ENTREP2 p.Val190Met (c.568G>A)?

AlphaMissense predicts likely pathogenic (score 0.8055) — an in-silico prediction, not a clinical call.

ENTREP2 p.Val190Met

c.568G>A · rs369693273 · VCV2454929

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8055 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0687%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8055	likely pathogenic
REVEL	0.302	indeterminate
SaProt	LLR -9.42	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 5.8	GERP 0.78, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 447 kb · p 0.2 · regional, not allelic
Overall
CADD	28.8	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 0.0687% European (non-Finnish) · 788/1,147,012 alleles

Filtering AF 0.0647% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0631%

Overall 0.0538% 835/1,551,420 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0687%	1,456
Finnishnot grpmax-eligible	0.0335%	2,986
Remaining individualsnot grpmax-eligible	0.0316%	3,164
Admixed American	0.00981%	10,198
African / African-American	0.00411%	24,341

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: ENTREP2
Protein: p.Val190Met
Coding: c.568G>A
MANE Select: NM_015307
dbSNP: rs369693273
Type: single nucleotide variant
Location: chr15:29151796 (GRCh38)
Structure: AlphaFold pLDDT 59.09

Full ENTREP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NSMCE3 p.Gly190= Likely benign ★ same residue
ENTREP2 p.Gly126Ser Uncertain significance ★★ ⚠ same type
NSMCE3 p.Ala293Thr Uncertain significance ★★ ⚠ same type
NSMCE3 p.Arg133Ser Uncertain significance ★★ ⚠ same type
NSMCE3 p.Gln14His Uncertain significance ★★ ⚠ same type
NSMCE3 p.Glu45Gln Uncertain significance ★★ ⚠ same type
NSMCE3 p.Gly78Arg Uncertain significance ★★ ⚠ same type
NSMCE3 p.Ile193Val 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/entrep2-p-val190met (accessed [today's date]).

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