Is CD244 p.Ile229Val (c.685A>G) pathogenic?

CD244 p.Ile229Val (c.685A>G) is classified Benign in CD244 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-29). AlphaMissense: likely benign (0.0684); Low-frequency (popmax 2.39%, afr).

How common is CD244 p.Ile229Val (c.685A>G) in the general population?

CD244 p.Ile229Val (c.685A>G) is low-frequency (popmax 2.39%, afr) (gnomAD).

What do computational predictors say about CD244 p.Ile229Val (c.685A>G)?

AlphaMissense predicts likely benign (score 0.0684) — an in-silico prediction, not a clinical call.

CD244 p.Ile229Val

c.685A>G · rs76030314 · VCV784959

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0684 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.39%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0684	likely benign
REVEL	0.002	strongly benign-leaning
SaProt	LLR -6.42	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 -2.2	GERP -2.3
Regional constraint	o/e 0.95	unconstrained · MANE · 31 kb · p 0.33 · regional, not allelic
Overall
CADD	0.081	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 I234V vs ClinVar I229V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.39% African / African-American · 1,791/75,008 alleles

Filtering AF 2.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.26%

Overall 0.127% 2,044/1,613,928 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.39%	42
Remaining individualsnot grpmax-eligible	0.17%	590
Middle Eastern	0.132%	757
Ashkenazi Jewishnot grpmax-eligible	0.128%	779
Admixed American	0.122%	822
South Asian	0.0143%	7,003
European (non-Finnish)	0.00127%	78,663

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.Ile229Val
Coding: c.685A>G
MANE Select: NM_016382
dbSNP: rs76030314
Type: single nucleotide variant
Location: chr1:160839020 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 71.23

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.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
CD244 p.Asn349Lys 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-ile229val (accessed [today's date]).

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