Is CHD4 p.Pro148Arg (c.443C>G) pathogenic?

CHD4 p.Pro148Arg (c.443C>G) is classified Likely benign in CHD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely pathogenic (0.9084); Absent from gnomAD v4.1.

How common is CHD4 p.Pro148Arg (c.443C>G) in the general population?

CHD4 p.Pro148Arg (c.443C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD4 p.Pro148Arg (c.443C>G)?

AlphaMissense predicts likely pathogenic (score 0.9084) — an in-silico prediction, not a clinical call.

CHD4 p.Pro148Arg

c.443C>G · rs2540414981 · VCV2873299

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9084 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9084	likely pathogenic
REVEL	0.577	indeterminate
SaProt	LLR -7.28	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.77, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 520 bp · p 3.2e-07 · regional, not allelic
Overall
CADD	26.6	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

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.Pro148Arg
Coding: c.443C>G
MANE Select: NM_001273
dbSNP: rs2540414981
Type: single nucleotide variant
Location: chr12:6601762 (GRCh38)
Gene constraint: LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 65.41 · 12 PDB
Residue 148: the 'disordered' region; an α-helix

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

Similar variants

CHD4 p.Pro148Leu Uncertain significance ★ ⚠ 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-pro148arg (accessed [today's date]).

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