Is CD244 p.Asn349Lys (c.1047C>G) pathogenic?

CD244 p.Asn349Lys (c.1047C>G) is classified Uncertain significance in CD244 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely benign (0.2069); Very rare (popmax 0.00333%, amr).

How common is CD244 p.Asn349Lys (c.1047C>G) in the general population?

CD244 p.Asn349Lys (c.1047C>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CD244 p.Asn349Lys (c.1047C>G)?

AlphaMissense predicts likely benign (score 0.2069) — an in-silico prediction, not a clinical call.

CD244 p.Asn349Lys

c.1047C>G · VCV4650538

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2069 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2069	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -5.10	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 0.13	GERP -0.66, phastCons 0.001
Regional constraint	o/e 0.95	unconstrained · MANE · 31 kb · p 0.33 · regional, not allelic
Overall
CADD	20.4	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM N354K vs ClinVar N349K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,006 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000558% 9/1,614,014 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,003
African / African-American	0.00267%	37,464
European (non-Finnish)	0.000424%	235,992

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.Asn349Lys
Coding: c.1047C>G
MANE Select: NM_016382
Type: single nucleotide variant
Location: chr1:160831398 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 71.23
Residue 349: the 'disordered' region

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

Similar variants

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
CD244 p.Arg355His 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-asn349lys (accessed [today's date]).

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