Is CHDH p.Ile299Val (c.895A>G) pathogenic?

CHDH p.Ile299Val (c.895A>G) is classified Uncertain significance in CHDH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-08). AlphaMissense: likely benign (0.0933); Very rare (popmax 0.00729%, nfe).

How common is CHDH p.Ile299Val (c.895A>G) in the general population?

CHDH p.Ile299Val (c.895A>G) is very rare (popmax 0.00729%, nfe) (gnomAD).

What do computational predictors say about CHDH p.Ile299Val (c.895A>G)?

AlphaMissense predicts likely benign (score 0.0933) — an in-silico prediction, not a clinical call.

CHDH p.Ile299Val

c.895A>G · rs773766584 · VCV2204929

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0933 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00729%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0933	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.9	GERP 0.74, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 6,228 bp · p 0.86 · regional, not allelic
Overall
CADD	19.95	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 0.00729% European (non-Finnish) · 86/1,179,954 alleles

Filtering AF 0.00604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00539% 87/1,613,872 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00729%	13,720
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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: CHDH
Protein: p.Ile299Val
Coding: c.895A>G
MANE Select: NM_018397
dbSNP: rs773766584
Type: single nucleotide variant
Location: chr3:53821737 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.84

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

Similar variants

CHDH p.Pro396Leu Uncertain significance ★★ ⚠ same type
CHDH c.704-3C>T Benign ★★ same type
CHDH p.Gly235= Benign ★★ same type
CHDH p.Val45= Benign ★★ same type
CHDH p.Ala13Val Uncertain significance ★ ⚠ same type
CHDH p.Ala170Thr Uncertain significance ★ ⚠ same type
CHDH p.Ala177Thr Uncertain significance ★ ⚠ same type
CHDH p.Ala240Val 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/chdh-p-ile299val (accessed [today's date]).

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