Is CD244 p.Ile86Val (c.256A>G) pathogenic?

CD244 p.Ile86Val (c.256A>G) is classified Uncertain significance in CD244 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). AlphaMissense: likely benign (0.0943); Very rare (popmax 0.00167%, amr).

How common is CD244 p.Ile86Val (c.256A>G) in the general population?

CD244 p.Ile86Val (c.256A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CD244 p.Ile86Val (c.256A>G)?

AlphaMissense predicts likely benign (score 0.0943) — an in-silico prediction, not a clinical call.

CD244 p.Ile86Val

c.256A>G · VCV3998137

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0943 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0943	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -5.81	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 -1.2	GERP -2.5
Regional constraint	o/e 0.95	unconstrained · MANE · 31 kb · p 0.33 · regional, not allelic
Overall
CADD	0.115	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 0.00167% Admixed American · 1/60,002 alleles

Overall 0.000124% 2/1,614,080 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,002
European (non-Finnish)	8.47e-05%	1,180,012

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.Ile86Val
Coding: c.256A>G
MANE Select: NM_016382
Type: single nucleotide variant
Location: chr1:160841707 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 71.23
Residue 86: 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-ile86val (accessed [today's date]).

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