Is CD248 p.Ala303Val (c.908C>T) pathogenic?

CD248 p.Ala303Val (c.908C>T) is classified Likely benign in CD248 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-15). AlphaMissense: likely benign (0.1909); Low-frequency (popmax 1.35%, mid).

How common is CD248 p.Ala303Val (c.908C>T) in the general population?

CD248 p.Ala303Val (c.908C>T) is low-frequency (popmax 1.35%, mid) (gnomAD).

What do computational predictors say about CD248 p.Ala303Val (c.908C>T)?

AlphaMissense predicts likely benign (score 0.1909) — an in-silico prediction, not a clinical call.

CD248 p.Ala303Val

c.908C>T · rs150281243 · VCV770401

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1909 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.35%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1909	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -9.96	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 9.8	GERP 0.28, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 942 bp · p 0.041 · regional, not allelic
Overall
CADD	19.52	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 1.35% Middle Eastern · 82/6,062 alleles

Filtering AF 1.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.03%

Overall 0.776% 12,519/1,613,260 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.35%	74
Ashkenazi Jewishnot grpmax-eligible	1.33%	75
European (non-Finnish)	0.888%	113
Remaining individualsnot grpmax-eligible	0.702%	142
Finnishnot grpmax-eligible	0.656%	153
Admixed American	0.655%	153
Amishnot grpmax-eligible	0.219%	456
South Asian	0.201%	498
African / African-American	0.176%	568
East Asian	0.0134%	7,479

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.Ala303Val
Coding: c.908C>T
MANE Select: NM_020404
dbSNP: rs150281243
Type: single nucleotide variant
Location: chr11:66316120 (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.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
CD248 p.Val447= 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-ala303val (accessed [today's date]).

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