Is CD96 p.Asn557= (c.1671C>T) pathogenic?

CD96 p.Asn557= (c.1671C>T) is classified Benign/Likely benign in CD96 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-15). Rare (popmax 0.648%, afr).

How common is CD96 p.Asn557= (c.1671C>T) in the general population?

CD96 p.Asn557= (c.1671C>T) is rare (popmax 0.648%, afr) (gnomAD).

CD96 p.Asn557=

c.1671C>T · rs148525569 · VCV342548

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.648%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.41	GERP -3.9
Overall
CADD	1.252	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.648% African / African-American · 486/75,050 alleles

Filtering AF 0.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.581%

Overall 0.0469% 756/1,613,544 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.648%	154
Middle Eastern	0.397%	252
Remaining individualsnot grpmax-eligible	0.134%	744
Admixed American	0.0949%	1,053
European (non-Finnish)	0.00822%	12,159
South Asian	0.00769%	13,011
East Asian	0.00223%	44,888

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.Asn557=
Coding: c.1671C>T
MANE Select: NM_005816
dbSNP: rs148525569
Type: single nucleotide variant
Location: chr3:111649767 (GRCh38)
Gene constraint: LOEUF 1.16 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.81 · 1 PDB

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-asn557 (accessed [today's date]).

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