Is CD248 p.Val254Met (c.760G>A) pathogenic?

CD248 p.Val254Met (c.760G>A) is classified Uncertain significance in CD248 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-09). AlphaMissense: likely benign (0.197); Ultra-rare (popmax 0.0489%, nfe).

How common is CD248 p.Val254Met (c.760G>A) in the general population?

CD248 p.Val254Met (c.760G>A) is ultra-rare (popmax 0.0489%, nfe) (gnomAD).

What do computational predictors say about CD248 p.Val254Met (c.760G>A)?

AlphaMissense predicts likely benign (score 0.197) — an in-silico prediction, not a clinical call.

CD248 p.Val254Met

c.760G>A · rs202021533 · VCV2348599

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.197 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0489%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.197	likely benign
REVEL	0.155	moderately benign-leaning
SaProt	LLR -11.16	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.21, phastCons 0.94
Regional constraint	o/e 0.90	unconstrained · MANE · 942 bp · p 0.041 · regional, not allelic
Overall
CADD	17.17	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 0.0489% European (non-Finnish) · 577/1,179,930 alleles

Filtering AF 0.0456% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0443%

Overall 0.0384% 619/1,613,522 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0489%	2,045
Remaining individualsnot grpmax-eligible	0.0304%	3,289
Finnishnot grpmax-eligible	0.0189%	5,293
Middle Eastern	0.0165%	6,062
African / African-American	0.00933%	10,722
Admixed American	0.00333%	30,011
South Asian	0.0011%	91,080

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.Val254Met
Coding: c.760G>A
MANE Select: NM_020404
dbSNP: rs202021533
Type: single nucleotide variant
Location: chr11:66316268 (GRCh38)
Gene constraint: LOEUF 1.594 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.70

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-val254met (accessed [today's date]).

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