Is CD96 p.Thr44Ile (c.131C>T) pathogenic?

CD96 p.Thr44Ile (c.131C>T) is classified Likely benign in CD96 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). AlphaMissense: likely benign (0.1997); Rare (popmax 0.348%, sas).

How common is CD96 p.Thr44Ile (c.131C>T) in the general population?

CD96 p.Thr44Ile (c.131C>T) is rare (popmax 0.348%, sas) (gnomAD).

What do computational predictors say about CD96 p.Thr44Ile (c.131C>T)?

AlphaMissense predicts likely benign (score 0.1997) — an in-silico prediction, not a clinical call.

CD96 p.Thr44Ile

c.131C>T · rs557620368 · VCV2715386

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1997 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.348%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1997	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -8.65	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 0.083	GERP 2, phastCons 0.002
Regional constraint	o/e 1.10	unconstrained · MANE · 108 kb · p 0.013 · regional, not allelic
Overall
CADD	18.61	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 0.348% South Asian · 317/91,082 alleles

Filtering AF 0.316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.304%

Overall 0.0206% 332/1,614,190 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.348%	287
Remaining individualsnot grpmax-eligible	0.0176%	5,682
Middle Eastern	0.0165%	6,062
Admixed American	0.00167%	60,026
European (non-Finnish)	0.000169%	590,016

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.Thr44Ile
Coding: c.131C>T
MANE Select: NM_005816
dbSNP: rs557620368
Type: single nucleotide variant
Location: chr3:111545115 (GRCh38)
Gene constraint: LOEUF 1.16 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.81 · 1 PDB
Residue 44: a β-strand; the ig-like v-type 1 domain

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

Similar variants

ZBED2 p.Thr44Pro 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-thr44ile (accessed [today's date]).

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