Is CHD4 p.Pro799Ala (c.2395C>G) pathogenic?

CHD4 p.Pro799Ala (c.2395C>G) is classified Likely benign in CHD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-11). AlphaMissense: likely pathogenic (0.7421); Very rare (popmax 8.47e-05%, nfe).

How common is CHD4 p.Pro799Ala (c.2395C>G) in the general population?

CHD4 p.Pro799Ala (c.2395C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CHD4 p.Pro799Ala (c.2395C>G)?

AlphaMissense predicts likely pathogenic (score 0.7421) — an in-silico prediction, not a clinical call.

CHD4 p.Pro799Ala

c.2395C>G · VCV4915392

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7421 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7421	likely pathogenic
REVEL	0.944	strongly pathogenic-leaning
SaProt	LLR -14.59	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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 0.45	unconstrained · MANE · 1,707 bp · p 2.5e-13 · regional, not allelic
Overall
CADD	31.0	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 8.47e-05% European (non-Finnish) · 1/1,180,026 alleles

Overall 6.84e-05% 1/1,461,892 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.Pro799Ala
Coding: c.2395C>G
MANE Select: NM_001273
Type: single nucleotide variant
Location: chr12:6593535 (GRCh38)
Gene constraint: LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 65.41 · 12 PDB
Residue 799: the helicase atp-binding domain

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

Similar variants

CHD4 p.Pro799= Benign/Likely benign ★★ same residue
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

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-pro799ala (accessed [today's date]).

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