Is CD248 p.Arg712Ser (c.2134C>A) pathogenic?

CD248 p.Arg712Ser (c.2134C>A) is classified Uncertain significance in CD248 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). AlphaMissense: ambiguous (0.5622); Absent from gnomAD v4.1.

How common is CD248 p.Arg712Ser (c.2134C>A) in the general population?

CD248 p.Arg712Ser (c.2134C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD248 p.Arg712Ser (c.2134C>A)?

AlphaMissense predicts ambiguous (score 0.5622) — an in-silico prediction, not a clinical call.

CD248 p.Arg712Ser

c.2134C>A · VCV3264786

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5622 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5622	ambiguous
REVEL	0.371	indeterminate
SaProt	LLR -8.84	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	24.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD248
Protein: p.Arg712Ser
Coding: c.2134C>A
MANE Select: NM_020404
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.Arg712Cys Uncertain significance ★ ⚠ same residue
CD248 p.Arg712His 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-arg712ser (accessed [today's date]).

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