Is CD248 p.Glu53Asp (c.159G>C) pathogenic?

CD248 p.Glu53Asp (c.159G>C) is classified Uncertain significance in CD248 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). AlphaMissense: likely benign (0.1519); Ultra-rare (popmax 0.0918%, afr).

How common is CD248 p.Glu53Asp (c.159G>C) in the general population?

CD248 p.Glu53Asp (c.159G>C) is ultra-rare (popmax 0.0918%, afr) (gnomAD).

What do computational predictors say about CD248 p.Glu53Asp (c.159G>C)?

AlphaMissense predicts likely benign (score 0.1519) — an in-silico prediction, not a clinical call.

CD248 p.Glu53Asp

c.159G>C · rs749572714 · VCV2460142

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1519 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0918%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1519	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -6.11	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 0.27	GERP -2.4, phastCons 0.87
Regional constraint	o/e 0.90	unconstrained · MANE · 942 bp · p 0.041 · regional, not allelic
Overall
CADD	18.4	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 0.0918% African / African-American · 67/72,996 alleles

Filtering AF 0.0741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0677%

Overall 0.00465% 72/1,547,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0918%	1,089
Middle Eastern	0.0221%	4,522
Remaining individualsnot grpmax-eligible	0.00668%	14,975

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.Glu53Asp
Coding: c.159G>C
MANE Select: NM_020404
dbSNP: rs749572714
Type: single nucleotide variant
Location: chr11:66316869 (GRCh38)
Gene constraint: LOEUF 1.594 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.70
Residue 53: the c-type lectin domain

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

Similar variants

CD248 p.Glu53Lys 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
CD248 p.Ser598= 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-glu53asp (accessed [today's date]).

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