Is CD48 p.Leu16= (c.46C>T) pathogenic?

CD48 p.Leu16= (c.46C>T) is classified Benign in CD48 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-20). Common (popmax 5.52%, sas) — too common for a highly-penetrant pathogenic allele.

CD48 p.Leu16=

Q: How common is CD48 p.Leu16= (c.46C>T) in the general population?

CD48 p.Leu16= (c.46C>T) is common (popmax 5.52%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.46C>T · VCV4683734

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 5.52%, sas) — 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 1.4	GERP -0.33, phastCons 0.58
Overall
CADD	4.135	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.52% South Asian · 5,022/91,052 alleles

Filtering AF 5.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.34%

Overall 2.27% 36,672/1,613,554 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	5.52%	18
European (non-Finnish)	2.36%	42
Middle Eastern	2.15%	47
Remaining individualsnot grpmax-eligible	2.01%	50
East Asian	1.65%	61
Finnishnot grpmax-eligible	1.48%	67
Admixed American	0.761%	131
African / African-American	0.34%	294
Ashkenazi Jewishnot grpmax-eligible	0.237%	423

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.Leu16=
Coding: c.46C>T
MANE Select: NM_001778
Type: single nucleotide variant
Location: chr1:160711718 (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-leu16 (accessed [today's date]).

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