Is CD48 p.Trp69Arg (c.205T>C) pathogenic?

CD48 p.Trp69Arg (c.205T>C) is classified Likely benign in CD48 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-01). AlphaMissense: ambiguous (0.5486); Rare (popmax 0.927%, eas).

How common is CD48 p.Trp69Arg (c.205T>C) in the general population?

CD48 p.Trp69Arg (c.205T>C) is rare (popmax 0.927%, eas) (gnomAD).

What do computational predictors say about CD48 p.Trp69Arg (c.205T>C)?

AlphaMissense predicts ambiguous (score 0.5486) — an in-silico prediction, not a clinical call.

CD48 p.Trp69Arg

c.205T>C · rs143226582 · VCV2639505

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5486 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.927%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5486	ambiguous
REVEL	0.199	benign-leaning
SaProt	LLR -9.44	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.25	GERP -0.64
Regional constraint	o/e 1.07	unconstrained · MANE · 33 kb · p 0.23 · regional, not allelic
Overall
CADD	15.14	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.927% East Asian · 416/44,894 alleles

Filtering AF 0.853% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.824%

Overall 0.0282% 456/1,614,252 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.927%	108
Remaining individualsnot grpmax-eligible	0.04%	2,500
South Asian	0.00988%	10,121
Admixed American	0.00167%	60,032
European (non-Finnish)	0.000424%	236,008

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.Trp69Arg
Coding: c.205T>C
MANE Select: NM_001778
dbSNP: rs143226582
Type: single nucleotide variant
Location: chr1:160685067 (GRCh38)
Gene constraint: LOEUF 1.31 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.20 · 1 PDB
Residue 69: a β-strand; 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-trp69arg (accessed [today's date]).

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