Is CD248 p.Arg712Cys (c.2134C>T) pathogenic?

CD248 p.Arg712Cys (c.2134C>T) is classified Uncertain significance in CD248 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-10). AlphaMissense: ambiguous (0.4295); Very rare (popmax 0.00935%, afr).

How common is CD248 p.Arg712Cys (c.2134C>T) in the general population?

CD248 p.Arg712Cys (c.2134C>T) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about CD248 p.Arg712Cys (c.2134C>T)?

AlphaMissense predicts ambiguous (score 0.4295) — an in-silico prediction, not a clinical call.

CD248 p.Arg712Cys

c.2134C>T · rs747726735 · VCV2271677

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4295 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Computational evidence

Protein change
AlphaMissense	0.4295	ambiguous
REVEL	0.629	indeterminate
SaProt	LLR -6.39	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 1,284 bp · p 0.02 · regional, not allelic
Overall
CADD	32.0	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 0.00935% African / African-American · 7/74,898 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00136% 22/1,612,022 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,700
Finnishnot grpmax-eligible	0.00158%	63,482
European (non-Finnish)	0.0011%	90,726
South Asian	0.0011%	90,814

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.Arg712Cys
Coding: c.2134C>T
MANE Select: NM_020404
dbSNP: rs747726735
Type: single nucleotide variant
Location: chr11:66314894 (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.Arg712His Uncertain significance ★ ⚠ same residue
CD248 p.Arg712Ser Uncertain significance ★ ⚠ same residue
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

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-arg712cys (accessed [today's date]).

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