Is CD244 p.Ile44Met (c.132A>G) pathogenic?

CD244 p.Ile44Met (c.132A>G) is classified Uncertain significance in CD244 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely benign (0.0998); Ultra-rare (popmax 0.0348%, nfe).

How common is CD244 p.Ile44Met (c.132A>G) in the general population?

CD244 p.Ile44Met (c.132A>G) is ultra-rare (popmax 0.0348%, nfe) (gnomAD).

What do computational predictors say about CD244 p.Ile44Met (c.132A>G)?

AlphaMissense predicts likely benign (score 0.0998) — an in-silico prediction, not a clinical call.

CD244 p.Ile44Met

c.132A>G · rs140915491 · VCV2244838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0998 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0348%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0998	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -8.02	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 -0.33	GERP -2.5
Regional constraint	o/e 0.95	unconstrained · MANE · 31 kb · p 0.33 · regional, not allelic
Overall
CADD	1.579	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 0.0348% European (non-Finnish) · 411/1,180,010 alleles

Filtering AF 0.032% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0309%

Overall 0.0293% 473/1,614,022 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0671%	1,489
European (non-Finnish)grpmax	0.0348%	2,871
Admixed American	0.0133%	7,500
Remaining individualsnot grpmax-eligible	0.0096%	10,414
African / African-American	0.00668%	14,981

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile44Met
Coding: c.132A>G
MANE Select: NM_016382
dbSNP: rs140915491
Type: single nucleotide variant
Location: chr1:160841831 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 71.23
Residue 44: the ig-like 1 domain

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-ile44met (accessed [today's date]).

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