Is CD276 p.Glu273Lys (c.817G>A) pathogenic?

CD276 p.Glu273Lys (c.817G>A) is classified Uncertain significance in CD276 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely benign (0.0741); Very rare (popmax 0.00223%, eas).

How common is CD276 p.Glu273Lys (c.817G>A) in the general population?

CD276 p.Glu273Lys (c.817G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CD276 p.Glu273Lys (c.817G>A)?

AlphaMissense predicts likely benign (score 0.0741) — an in-silico prediction, not a clinical call.

CD276 p.Glu273Lys

c.817G>A · rs776686900 · VCV2455022

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0741 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0741	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -11.74	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.78 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4	GERP 0.46, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 13 kb · p 0.0018 · regional, not allelic
Overall
CADD	23.9	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 0.00223% East Asian · 1/44,866 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,613,318 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,866
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.000678%	147,500

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: CD276
Protein: p.Glu273Lys
Coding: c.817G>A
MANE Select: NM_001024736
dbSNP: rs776686900
Type: single nucleotide variant
Location: chr15:73703742 (GRCh38)
Gene constraint: LOEUF 0.888 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.63 · 3 PDB
Residue 273: a disulfide bond; the ig-like v-type 2 domain

Full CD276 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD276 p.Leu419= Benign ★★ same type
CD276 p.Ala132Ser Uncertain significance ★ ⚠ same type
CD276 p.Ala139Ser Uncertain significance ★ ⚠ same type
CD276 p.Ala28Ser Uncertain significance ★ ⚠ same type
CD276 p.Ala312Thr Uncertain significance ★ ⚠ same type
CD276 p.Ala350Thr Uncertain significance ★ ⚠ same type
CD276 p.Ala351Val Uncertain significance ★ ⚠ same type
CD276 p.Ala432Gly 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/cd276-p-glu273lys (accessed [today's date]).

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