Is CD248 p.Arg449Gln (c.1346G>A) pathogenic?

CD248 p.Arg449Gln (c.1346G>A) is classified Uncertain significance in CD248 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-13). AlphaMissense: likely benign (0.0858); Very rare (popmax 0.00988%, sas).

How common is CD248 p.Arg449Gln (c.1346G>A) in the general population?

CD248 p.Arg449Gln (c.1346G>A) is very rare (popmax 0.00988%, sas) (gnomAD).

What do computational predictors say about CD248 p.Arg449Gln (c.1346G>A)?

AlphaMissense predicts likely benign (score 0.0858) — an in-silico prediction, not a clinical call.

CD248 p.Arg449Gln

c.1346G>A · VCV3998145

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0858 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0858	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -4.46	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 0.21	GERP -3.3, phastCons 0.035
Regional constraint	o/e 0.90	unconstrained · MANE · 1,284 bp · p 0.02 · regional, not allelic
Overall
CADD	9.64	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 0.00988% South Asian · 9/91,060 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.00384% 62/1,613,368 alleles · very rare exomes 56/1,461,424 · genomes 6/151,944 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00988%	10,118
Admixed American	0.00667%	14,994
European (non-Finnish)	0.00373%	26,812
Remaining individualsnot grpmax-eligible	0.0032%	31,235
African / African-American	0.00267%	37,442
Finnishnot grpmax-eligible	0.00157%	63,854

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.Arg449Gln
Coding: c.1346G>A
MANE Select: NM_020404
Type: single nucleotide variant
Location: chr11:66315682 (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.Arg449Trp 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-arg449gln (accessed [today's date]).

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