Is CD96 p.Arg271Gly (c.811A>G) pathogenic?

CD96 p.Arg271Gly (c.811A>G) is classified Likely benign in CD96 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-26). AlphaMissense: likely benign (0.1163); Rare (popmax 0.667%, afr).

How common is CD96 p.Arg271Gly (c.811A>G) in the general population?

CD96 p.Arg271Gly (c.811A>G) is rare (popmax 0.667%, afr) (gnomAD).

What do computational predictors say about CD96 p.Arg271Gly (c.811A>G)?

AlphaMissense predicts likely benign (score 0.1163) — an in-silico prediction, not a clinical call.

CD96 p.Arg271Gly

c.811A>G · rs141120514 · VCV709665

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1163 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.667%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1163	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -10.79	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.5	GERP -0.82, phastCons 0.99
Regional constraint	o/e 1.10	unconstrained · MANE · 108 kb · p 0.013 · regional, not allelic
Overall
CADD	18.29	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R287G vs ClinVar R271G) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.667% African / African-American · 467/70,026 alleles

Filtering AF 0.617% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.597%

Overall 0.0405% 553/1,365,244 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.667%	150
Remaining individualsnot grpmax-eligible	0.0888%	1,126
Admixed American	0.0452%	2,213
South Asian	0.00814%	12,283
European (non-Finnish)	0.000419%	238,401

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: CD96
Protein: p.Arg271Gly
Coding: c.811A>G
MANE Select: NM_005816
dbSNP: rs141120514
Type: single nucleotide variant
Location: chr3:111598123 (GRCh38)
Gene constraint: LOEUF 1.16 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.81 · 1 PDB
Residue 271: the ig-like c2-type domain

Full CD96 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD96 c.1249+1G>A Uncertain significance ★★ same type
CD96 c.544-1512C>T Uncertain significance ★★ ⚠ same type
CD96 p.Asp205Gly Uncertain significance ★★ ⚠ same type
CD96 p.Asp224Asn Uncertain significance ★★ ⚠ same type
CD96 p.Ile151Thr Uncertain significance ★★ ⚠ same type
CD96 p.Leu120Pro Uncertain significance ★★ ⚠ same type
CD96 p.Lys500Arg Uncertain significance ★★ ⚠ same type
CD96 p.Pro346Ser 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/cd96-p-arg271gly (accessed [today's date]).

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