Is CD48 p.Leu30= (c.88T>C) pathogenic?

CD48 p.Leu30= (c.88T>C) is classified Benign in CD48 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-06). Common (popmax 5.27%, afr) — too common for a highly-penetrant pathogenic allele.

CD48 p.Leu30=

Q: How common is CD48 p.Leu30= (c.88T>C) in the general population?

CD48 p.Leu30= (c.88T>C) is common (popmax 5.27%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.88T>C · rs35918317 · VCV780270

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.27%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.13	GERP -3.2
Overall
CADD	1.159	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.27% African / African-American · 3,938/74,770 alleles

Filtering AF 5.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.07%

Overall 0.276% 4,425/1,603,824 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.27%	19
Admixed American	0.346%	289
Remaining individualsnot grpmax-eligible	0.326%	307
Middle Eastern	0.234%	428
South Asian	0.00554%	18,043
European (non-Finnish)	0.00512%	19,547

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.Leu30=
Coding: c.88T>C
MANE Select: NM_001778
dbSNP: rs35918317
Type: single nucleotide variant
Location: chr1:160685184 (GRCh38)
Gene constraint: LOEUF 1.31 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.20 · 1 PDB
Residue 30: the ig-like c2-type 1 domain

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.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
CD48 p.Asn44Ile 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-leu30 (accessed [today's date]).

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