Is CD48 p.Gln126Arg (c.377A>G) pathogenic?

CD48 p.Gln126Arg (c.377A>G) is classified Uncertain significance in CD48 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely benign (0.1019); Very rare (popmax 8.47e-05%, nfe).

How common is CD48 p.Gln126Arg (c.377A>G) in the general population?

CD48 p.Gln126Arg (c.377A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CD48 p.Gln126Arg (c.377A>G)?

AlphaMissense predicts likely benign (score 0.1019) — an in-silico prediction, not a clinical call.

CD48 p.Gln126Arg

c.377A>G · rs377101847 · VCV2492485

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1019 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1019	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -6.68	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 -2.9	GERP 0.47
Regional constraint	o/e 1.07	unconstrained · MANE · 33 kb · p 0.23 · regional, not allelic
Overall
CADD	5.094	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 8.47e-05% European (non-Finnish) · 1/1,180,046 alleles

Overall 0.000657% 1/152,168 alleles · very rare

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.Gln126Arg
Coding: c.377A>G
MANE Select: NM_001778
dbSNP: rs377101847
Type: single nucleotide variant
Location: chr1:160684895 (GRCh38)
Gene constraint: LOEUF 1.31 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.20 · 1 PDB
Residue 126: the ig-like c2-type 1 domain; a β-strand

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-gln126arg (accessed [today's date]).

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