Is CD48 p.Gly92= (c.276C>T) pathogenic?

CD48 p.Gly92= (c.276C>T) is classified Benign in CD48 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-06). Common (popmax 30.2%, afr) — too common for a highly-penetrant pathogenic allele.

CD48 p.Gly92=

Q: How common is CD48 p.Gly92= (c.276C>T) in the general population?

CD48 p.Gly92= (c.276C>T) is common (popmax 30.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.276C>T · VCV4683733

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 30.2%, 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 -3.1	GERP -3.2
Overall
CADD	0.301	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.2% African / African-American · 22,623/74,918 alleles

Filtering AF 29.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 29.7%

Overall 21.6% 348,646/1,613,592 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	32.6%	3
African / African-Americangrpmax	30.2%	3
Admixed American	27.2%	4
Ashkenazi Jewishnot grpmax-eligible	25.6%	4
Middle Eastern	25%	4
South Asian	24.9%	4
Remaining individualsnot grpmax-eligible	22%	5
European (non-Finnish)	20.8%	5
Finnishnot grpmax-eligible	19.4%	5
East Asian	14.8%	7

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gly92=
Coding: c.276C>T
MANE Select: NM_001778
Type: single nucleotide variant
Location: chr1:160684996 (GRCh38)
Gene constraint: LOEUF 1.31 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.20 · 1 PDB
Residue 92: 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.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-gly92 (accessed [today's date]).

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