Is CD96 p.Gln193Pro (c.578A>C) pathogenic?

CD96 p.Gln193Pro (c.578A>C) is classified Benign in CD96 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-19). AlphaMissense: likely benign (0.0956); Low-frequency (popmax 1.94%, afr).

How common is CD96 p.Gln193Pro (c.578A>C) in the general population?

CD96 p.Gln193Pro (c.578A>C) is low-frequency (popmax 1.94%, afr) (gnomAD).

What do computational predictors say about CD96 p.Gln193Pro (c.578A>C)?

AlphaMissense predicts likely benign (score 0.0956) — an in-silico prediction, not a clinical call.

CD96 p.Gln193Pro

c.578A>C · rs61733706 · VCV342525

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0956 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.94%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0956	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -5.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.23	GERP -1
Regional constraint	o/e 1.10	unconstrained · MANE · 108 kb · p 0.013 · regional, not allelic
Overall
CADD	3.293	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 Q209P vs ClinVar Q193P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.94% African / African-American · 1,452/74,940 alleles

Filtering AF 1.85% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.82%

Overall 0.11% 1,775/1,609,162 alleles · low-frequency exomes 928/1,456,818 · genomes 847/152,344 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.94%	52
Admixed American	0.2%	500
Remaining individualsnot grpmax-eligible	0.139%	717
Middle Eastern	0.132%	756
South Asian	0.00989%	10,110
European (non-Finnish)	0.00842%	11,873

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.Gln193Pro
Coding: c.578A>C
MANE Select: NM_005816
dbSNP: rs61733706
Type: single nucleotide variant
Location: chr3:111579061 (GRCh38)
Gene constraint: LOEUF 1.16 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.81 · 1 PDB
Residue 209 UniProt numbering: the ig-like v-type 2 domain

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

Similar variants

CD96 p.Gln193His Uncertain significance ★ ⚠ same residue
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

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-gln193pro (accessed [today's date]).

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