Is CD48 p.Ile26Leu (c.76A>C) pathogenic?

CD48 p.Ile26Leu (c.76A>C) is classified Uncertain significance in CD48 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-26). AlphaMissense: likely benign (0.0987); Ultra-rare (popmax 0.0214%, afr).

How common is CD48 p.Ile26Leu (c.76A>C) in the general population?

CD48 p.Ile26Leu (c.76A>C) is ultra-rare (popmax 0.0214%, afr) (gnomAD).

What do computational predictors say about CD48 p.Ile26Leu (c.76A>C)?

AlphaMissense predicts likely benign (score 0.0987) — an in-silico prediction, not a clinical call.

CD48 p.Ile26Leu

c.76A>C · VCV3264848

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0987 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0987	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -6.95	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 -2.5	GERP -0.83
Regional constraint	o/e 1.07	unconstrained · MANE · 33 kb · p 0.23 · regional, not allelic
Overall
CADD	6.046	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0214% African / African-American · 16/74,854 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00174% 28/1,611,396 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0214%	4,678
Remaining individualsnot grpmax-eligible	0.00802%	12,474
Admixed American	0.00333%	29,995
European (non-Finnish)	0.000425%	235,530

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: CD48
Protein: p.Ile26Leu
Coding: c.76A>C
MANE Select: NM_001778
Type: single nucleotide variant
Location: chr1:160711688 (GRCh38)
Gene constraint: LOEUF 1.31 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.20 · 1 PDB

Full CD48 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD48 p.Thr216Ile Uncertain significance ★★ ⚠ same type
CD48 c.652+73G>T Benign ★★ same type
CD48 p.Gln90= Benign ★★ same type
CD48 p.Leu30= Benign ★★ same type
CD48 p.Thr233= Benign/Likely benign ★★ same type
CD48 p.Ala93Thr Uncertain significance ★ ⚠ same type
CD48 p.Arg192Met Uncertain significance ★ ⚠ same type
CD48 p.Asn178Lys 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/cd48-p-ile26leu (accessed [today's date]).

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