Is CD276 p.Pro97Ser (c.289C>T) pathogenic?

CD276 p.Pro97Ser (c.289C>T) is classified Uncertain significance in CD276 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-16). AlphaMissense: likely benign (0.1109); Very rare (popmax 0.005%, nfe).

How common is CD276 p.Pro97Ser (c.289C>T) in the general population?

CD276 p.Pro97Ser (c.289C>T) is very rare (popmax 0.005%, nfe) (gnomAD).

What do computational predictors say about CD276 p.Pro97Ser (c.289C>T)?

AlphaMissense predicts likely benign (score 0.1109) — an in-silico prediction, not a clinical call.

CD276 p.Pro97Ser

c.289C>T · VCV4222763

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1109 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1109	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -11.65	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.32, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 13 kb · p 0.0018 · regional, not allelic
Overall
CADD	16.33	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 0.005% European (non-Finnish) · 59/1,180,016 alleles

Filtering AF 0.00394% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00361%

Overall 0.00403% 65/1,613,624 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,620
European (non-Finnish)grpmax	0.005%	20,000
African / African-American	0.00133%	74,938
South Asian	0.0011%	91,090

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro97Ser
Coding: c.289C>T
MANE Select: NM_001024736
Type: single nucleotide variant
Location: chr15:73702464 (GRCh38)
Gene constraint: LOEUF 0.888 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.63 · 3 PDB
Residue 97: a disulfide bond; a UniProt-annotated variant site (in); the ig-like v-type 1 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-pro97ser (accessed [today's date]).

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