Is CD248 p.Thr587Pro (c.1759A>C) pathogenic?

CD248 p.Thr587Pro (c.1759A>C) is classified Likely benign in CD248 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-13). AlphaMissense: likely benign (0.0709); Rare (popmax 0.211%, afr).

How common is CD248 p.Thr587Pro (c.1759A>C) in the general population?

CD248 p.Thr587Pro (c.1759A>C) is rare (popmax 0.211%, afr) (gnomAD).

What do computational predictors say about CD248 p.Thr587Pro (c.1759A>C)?

AlphaMissense predicts likely benign (score 0.0709) — an in-silico prediction, not a clinical call.

CD248 p.Thr587Pro

c.1759A>C · rs150334610 · VCV730132

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0709 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.211%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0709	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.2	GERP -0.63
Regional constraint	o/e 0.90	unconstrained · MANE · 1,284 bp · p 0.02 · regional, not allelic
Overall
CADD	0.553	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 0.211% African / African-American · 152/72,034 alleles

Filtering AF 0.184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.173%

Overall 0.011% 169/1,536,038 alleles · rare exomes 80/1,385,132 · genomes 89/150,906 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.211%	474
Admixed American	0.0244%	4,104
Remaining individualsnot grpmax-eligible	0.00847%	11,808

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.Thr587Pro
Coding: c.1759A>C
MANE Select: NM_020404
dbSNP: rs150334610
Type: single nucleotide variant
Location: chr11:66315269 (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-thr587pro (accessed [today's date]).

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