Is CD248 p.Arg42Cys (c.124C>T) pathogenic?

CD248 p.Arg42Cys (c.124C>T) is classified Uncertain significance in CD248 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: likely benign (0.2821); Ultra-rare (popmax 0.0634%, mid).

How common is CD248 p.Arg42Cys (c.124C>T) in the general population?

CD248 p.Arg42Cys (c.124C>T) is ultra-rare (popmax 0.0634%, mid) (gnomAD).

What do computational predictors say about CD248 p.Arg42Cys (c.124C>T)?

AlphaMissense predicts likely benign (score 0.2821) — an in-silico prediction, not a clinical call.

CD248 p.Arg42Cys

c.124C>T · VCV3829470

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2821 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0634%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2821	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -9.52	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 3.9	GERP 0.091, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 942 bp · p 0.041 · regional, not allelic
Overall
CADD	22.4	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 0.0634% Middle Eastern · 3/4,730 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00955%

Overall 0.0027% 42/1,558,300 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0634%	1,577
East Asian	0.0233%	4,286
Remaining individualsnot grpmax-eligible	0.00827%	12,087
South Asian	0.00579%	17,286
African / African-American	0.00273%	36,571
Admixed American	0.00186%	53,730
European (non-Finnish)	0.00138%	72,630

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: CD248
Protein: p.Arg42Cys
Coding: c.124C>T
MANE Select: NM_020404
Type: single nucleotide variant
Location: chr11:66316904 (GRCh38)
Gene constraint: LOEUF 1.594 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.70
Residue 42: the c-type lectin domain

Full CD248 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD248 p.Ala303Val Likely benign ★★ same type
CD248 p.Ala486Thr Benign ★★ same type
CD248 p.Arg101= Benign ★★ same type
CD248 p.Asp379= Benign ★★ same type
CD248 p.Ile485= Benign ★★ same type
CD248 p.Pro412= Benign ★★ same type
CD248 p.Ser598= Benign ★★ same type
CD248 p.Tyr410= Benign ★★ 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/cd248-p-arg42cys (accessed [today's date]).

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