Is CD244 p.Arg355Cys (c.1063C>T) pathogenic?

CD244 p.Arg355Cys (c.1063C>T) is classified Benign in CD244 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-08). AlphaMissense: likely benign (0.194); Low-frequency (popmax 2.01%, sas); Associated with CD244-related disorder.

What condition is associated with CD244 p.Arg355Cys (c.1063C>T)?

CD244 p.Arg355Cys (c.1063C>T) is associated with CD244-related disorder (ClinVar).

How common is CD244 p.Arg355Cys (c.1063C>T) in the general population?

CD244 p.Arg355Cys (c.1063C>T) is low-frequency (popmax 2.01%, sas) (gnomAD).

What do computational predictors say about CD244 p.Arg355Cys (c.1063C>T)?

AlphaMissense predicts likely benign (score 0.194) — an in-silico prediction, not a clinical call.

CD244 p.Arg355Cys

c.1063C>T · rs140746142 · VCV3037210

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.194 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.01%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CD244-related disorder

Computational evidence

Protein change
AlphaMissense	0.194	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -9.27	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 3.5	GERP 1.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 31 kb · p 0.33 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R360C vs ClinVar R355C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.01% South Asian · 1,828/91,074 alleles

Filtering AF 1.93% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9%

Overall 0.133% 2,152/1,614,104 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.01%	50
Middle Eastern	0.247%	404
Remaining individualsnot grpmax-eligible	0.139%	718
European (non-Finnish)	0.0176%	5,673
Admixed American	0.01%	10,004
East Asian	0.00891%	11,221
African / African-American	0.00533%	18,764

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: CD244
Protein: p.Arg355Cys
Coding: c.1063C>T
MANE Select: NM_016382
dbSNP: rs140746142
Type: single nucleotide variant
Location: chr1:160831382 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 71.23
Residue 355: the 'disordered' region

Full CD244 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CD244-related disorder

Similar variants

CD244 p.Arg355His Uncertain significance ★ ⚠ same residue
CD244 c.*578T>C Benign ★★ same type
CD244 p.Ile229Val Benign ★★ same type
CD244 p.Leu13= Benign ★★ same type
CD244 c.380-3C>T Uncertain significance ★ ⚠ same type
CD244 c.380-4C>T Uncertain significance ★ ⚠ same type
CD244 p.Ala234Ser Uncertain significance ★ ⚠ same type
CD244 p.Arg133Cys Uncertain significance ★ ⚠ 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/cd244-p-arg355cys (accessed [today's date]).

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