Is CHD4 p.Asp142Val (c.425A>T) pathogenic?

CHD4 p.Asp142Val (c.425A>T) is classified Uncertain significance in CHD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: likely benign (0.2433); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CHD4 p.Asp142Val (c.425A>T)?

CHD4 p.Asp142Val (c.425A>T) is associated with Inborn genetic diseases (ClinVar).

How common is CHD4 p.Asp142Val (c.425A>T) in the general population?

CHD4 p.Asp142Val (c.425A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD4 p.Asp142Val (c.425A>T)?

AlphaMissense predicts likely benign (score 0.2433) — an in-silico prediction, not a clinical call.

CHD4 p.Asp142Val

c.425A>T · VCV3266849

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2433 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2433	likely benign
REVEL	0.453	indeterminate
SaProt	LLR -8.75	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 7.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 4,403 bp · p 0.0078 · regional, not allelic
Overall
CADD	24.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHD4
Protein: p.Asp142Val
Coding: c.425A>T
MANE Select: NM_001273
Type: single nucleotide variant
Location: chr12:6601973 (GRCh38)
Gene constraint: LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 65.41 · 12 PDB
Residue 142: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD4 p.Arg1173Gln Pathogenic/Likely pathogenic ★★ same condition
CHD4 p.Ala1718Val Uncertain significance ★★ ⚠ same condition
CHD4 p.Arg1288Trp Uncertain significance ★★ ⚠ same condition
CHD4 p.Arg611His Uncertain significance ★★ ⚠ same condition
CHD4 p.Arg836Cys Uncertain significance ★★ ⚠ same condition
CHD4 p.Asp1395Glu Uncertain significance ★★ ⚠ same condition
CHD4 p.Asp1659Gly Uncertain significance ★★ ⚠ same condition
CHD4 p.Glu406Lys Uncertain significance ★★ ⚠ same condition

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-asp142val (accessed [today's date]).

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