Is CD244 p.Val184Ile (c.550G>A) pathogenic?

CD244 p.Val184Ile (c.550G>A) is classified Likely benign in CD244 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-20). AlphaMissense: likely benign (0.0853); Very rare (popmax 0.0011%, sas).

How common is CD244 p.Val184Ile (c.550G>A) in the general population?

CD244 p.Val184Ile (c.550G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CD244 p.Val184Ile (c.550G>A)?

AlphaMissense predicts likely benign (score 0.0853) — an in-silico prediction, not a clinical call.

CD244 p.Val184Ile

c.550G>A · VCV3487972

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0853 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0853	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -7.84	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 -2.6	GERP -2.2
Regional constraint	o/e 0.95	unconstrained · MANE · 31 kb · p 0.33 · regional, not allelic
Overall
CADD	0.006	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 V189I vs ClinVar V184I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,080 alleles

Overall 6.84e-05% 1/1,461,888 alleles · very rare

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.Val184Ile
Coding: c.550G>A
MANE Select: NM_016382
Type: single nucleotide variant
Location: chr1:160841315 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 71.23
Residue 184: a disulfide bond; the ig-like 2 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-val184ile (accessed [today's date]).

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