Is ENTREP2 p.Gly276Ser (c.826G>A) pathogenic?

ENTREP2 p.Gly276Ser (c.826G>A) is classified Likely benign in ENTREP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). AlphaMissense: likely benign (0.0552); Ultra-rare (popmax 0.0228%, sas).

How common is ENTREP2 p.Gly276Ser (c.826G>A) in the general population?

ENTREP2 p.Gly276Ser (c.826G>A) is ultra-rare (popmax 0.0228%, sas) (gnomAD).

What do computational predictors say about ENTREP2 p.Gly276Ser (c.826G>A)?

AlphaMissense predicts likely benign (score 0.0552) — an in-silico prediction, not a clinical call.

ENTREP2 p.Gly276Ser

c.826G>A · VCV3275577

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0552 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0228%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0552	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -4.33	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 1.8	GERP -0.46, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 447 kb · p 0.2 · regional, not allelic
Overall
CADD	13.71	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 0.0228% South Asian · 19/83,472 alleles

Filtering AF 0.0148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.00194% 30/1,548,128 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0228%	4,393
East Asian	0.00982%	10,181
Remaining individualsnot grpmax-eligible	0.00333%	30,003
African / African-American	0.00274%	36,447
European (non-Finnish)	0.000262%	382,045

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.Gly276Ser
Coding: c.826G>A
MANE Select: NM_015307
Type: single nucleotide variant
Location: chr15:29136467 (GRCh38)
Structure: AlphaFold pLDDT 59.09

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

Similar variants

NSMCE3 p.Lys276Glu 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-gly276ser (accessed [today's date]).

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