Is CD48 p.Leu241Ser (c.722T>C) pathogenic?

CD48 p.Leu241Ser (c.722T>C) is classified Benign in CD48 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-19). AlphaMissense: likely benign (0.2227); Low-frequency (popmax 3.55%, afr).

How common is CD48 p.Leu241Ser (c.722T>C) in the general population?

CD48 p.Leu241Ser (c.722T>C) is low-frequency (popmax 3.55%, afr) (gnomAD).

What do computational predictors say about CD48 p.Leu241Ser (c.722T>C)?

AlphaMissense predicts likely benign (score 0.2227) — an in-silico prediction, not a clinical call.

CD48 p.Leu241Ser

c.722T>C · VCV4683728

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2227 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.55%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2227	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -8.20	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 4.2	GERP 0.35, phastCons 0.79
Regional constraint	o/e 1.07	unconstrained · MANE · 33 kb · p 0.23 · regional, not allelic
Overall
CADD	18.65	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 3.55% African / African-American · 2,667/75,044 alleles

Filtering AF 3.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.4%

Overall 0.191% 3,087/1,613,778 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.55%	28
Admixed American	0.315%	318
Remaining individualsnot grpmax-eligible	0.261%	383
Middle Eastern	0.099%	1,010
South Asian	0.0275%	3,643
European (non-Finnish)	0.00314%	31,882

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.Leu241Ser
Coding: c.722T>C
MANE Select: NM_001778
Type: single nucleotide variant
Location: chr1:160679062 (GRCh38)
Gene constraint: LOEUF 1.31 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.20 · 1 PDB
Residue 241: a UniProt-annotated variant site (in)

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-leu241ser (accessed [today's date]).

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