Is ENTREP2 p.Met200Ile (c.600G>A) pathogenic?

ENTREP2 p.Met200Ile (c.600G>A) is classified Uncertain significance in ENTREP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely pathogenic (0.8018); Ultra-rare (popmax 0.0167%, mid).

How common is ENTREP2 p.Met200Ile (c.600G>A) in the general population?

ENTREP2 p.Met200Ile (c.600G>A) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about ENTREP2 p.Met200Ile (c.600G>A)?

AlphaMissense predicts likely pathogenic (score 0.8018) — an in-silico prediction, not a clinical call.

ENTREP2 p.Met200Ile

c.600G>A · rs891282780 · VCV3089206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8018 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8018	likely pathogenic
REVEL	0.224	benign-leaning
SaProt	LLR -5.62	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.72, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 447 kb · p 0.2 · regional, not allelic
Overall
CADD	23.2	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 0.0167% Middle Eastern · 1/5,994 alleles

Overall 7.15e-05% 1/1,399,526 alleles · ultra-rare

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.Met200Ile
Coding: c.600G>A
MANE Select: NM_015307
dbSNP: rs891282780
Type: single nucleotide variant
Location: chr15:29151764 (GRCh38)
Structure: AlphaFold pLDDT 59.09

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

Similar variants

NSMCE3 p.Asp200Gly Uncertain significance ★ ⚠ 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-met200ile (accessed [today's date]).

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