Is CD48 p.Cys193Tyr (c.578G>A) pathogenic?

CD48 p.Cys193Tyr (c.578G>A) is classified Uncertain significance in CD48 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: likely benign (0.2896); Absent from gnomAD v4.1.

How common is CD48 p.Cys193Tyr (c.578G>A) in the general population?

CD48 p.Cys193Tyr (c.578G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD48 p.Cys193Tyr (c.578G>A)?

AlphaMissense predicts likely benign (score 0.2896) — an in-silico prediction, not a clinical call.

CD48 p.Cys193Tyr

c.578G>A · VCV4222944

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2896 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2896	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -8.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	donor gain · deltas
Pangolin	Δ0.30	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.89	GERP -3.3
Regional constraint	o/e 1.07	unconstrained · MANE · 33 kb · p 0.23 · regional, not allelic
Overall
CADD	0.228	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD48
Protein: p.Cys193Tyr
Coding: c.578G>A
MANE Select: NM_001778
Type: single nucleotide variant
Location: chr1:160681276 (GRCh38)
Gene constraint: LOEUF 1.31 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.20 · 1 PDB
Residue 193: a disulfide bond; the ig-like c2-type 2 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-cys193tyr (accessed [today's date]).

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