Is CHD4 p.Ala230Val (c.689C>T) pathogenic?

CHD4 p.Ala230Val (c.689C>T) is classified Uncertain significance in CHD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-29). AlphaMissense: likely benign (0.222); Very rare (popmax 8.47e-05%, nfe).

How common is CHD4 p.Ala230Val (c.689C>T) in the general population?

CHD4 p.Ala230Val (c.689C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CHD4 p.Ala230Val (c.689C>T)?

AlphaMissense predicts likely benign (score 0.222) — an in-silico prediction, not a clinical call.

CHD4 p.Ala230Val

c.689C>T · rs2540414265 · VCV2663673

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.222 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.222	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -7.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 1,073 bp · p 0.009 · regional, not allelic
Overall
CADD	23.1	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 8.47e-05% European (non-Finnish) · 1/1,180,020 alleles

Overall 6.84e-05% 1/1,461,870 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: CHD4
Protein: p.Ala230Val
Coding: c.689C>T
MANE Select: NM_001273
dbSNP: rs2540414265
Type: single nucleotide variant
Location: chr12:6601399 (GRCh38)
Gene constraint: LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 65.41 · 12 PDB

Full CHD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD4 p.Arg1068His Pathogenic/Likely pathogenic ★★ same type
CHD4 p.Arg1173Gln Pathogenic/Likely pathogenic ★★ same type
CHD4 p.Arg1173Trp Pathogenic/Likely pathogenic ★★ same type
CHD4 p.Arg1177Cys Pathogenic/Likely pathogenic ★★ same type
CHD4 p.Arg1177His Pathogenic/Likely pathogenic ★★ same type
CHD4 p.Arg1183Cys Pathogenic/Likely pathogenic ★★ same type
CHD4 p.Arg1183His Pathogenic/Likely pathogenic ★★ same type
CHD4 p.Arg1340Cys Pathogenic ★★ 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/chd4-p-ala230val (accessed [today's date]).

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