Is CHUK p.Ile307Val (c.919A>G) pathogenic?

CHUK p.Ile307Val (c.919A>G) is classified Likely benign in CHUK (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-21). AlphaMissense: likely benign (0.1591); Rare (popmax 0.668%, afr).

How common is CHUK p.Ile307Val (c.919A>G) in the general population?

CHUK p.Ile307Val (c.919A>G) is rare (popmax 0.668%, afr) (gnomAD).

What do computational predictors say about CHUK p.Ile307Val (c.919A>G)?

AlphaMissense predicts likely benign (score 0.1591) — an in-silico prediction, not a clinical call.

CHUK p.Ile307Val

c.919A>G · rs141877809 · VCV785325

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1591 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.668%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1591	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -8.57	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 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.77 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.668% African / African-American · 501/75,054 alleles

Filtering AF 0.619% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.6%

Overall 0.0333% 537/1,614,136 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.668%	150
Remaining individualsnot grpmax-eligible	0.032%	3,125
Admixed American	0.0183%	5,457
South Asian	0.00329%	30,361
European (non-Finnish)	0.000169%	589,995

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: CHUK
Protein: p.Ile307Val
Coding: c.919A>G
MANE Select: NM_001278
dbSNP: rs141877809
Type: single nucleotide variant
Location: chr10:100218009 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI 0.39 (gnomAD)
Structure: AlphaFold pLDDT 84.41 · 5 PDB

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

Similar variants

CHUK p.Ile307= Likely benign ★ same residue
CHUK p.Arg365Gln Uncertain significance ★★ ⚠ same type
CHUK p.Arg424Cys Uncertain significance ★★ ⚠ same type
CHUK p.Arg563Cys Uncertain significance ★★ ⚠ same type
CHUK p.Arg563His Uncertain significance ★★ ⚠ same type
CHUK p.Gln226Pro Uncertain significance ★★ ⚠ same type
CHUK p.Gly346Arg Uncertain significance ★★ ⚠ same type
CHUK p.His520Arg 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/chuk-p-ile307val (accessed [today's date]).

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