Is CHD6 p.Arg74Trp (c.220A>T) pathogenic?

CHD6 p.Arg74Trp (c.220A>T) is classified Uncertain significance in CHD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-31). AlphaMissense: likely benign (0.104); Absent from gnomAD v4.1.

How common is CHD6 p.Arg74Trp (c.220A>T) in the general population?

CHD6 p.Arg74Trp (c.220A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD6 p.Arg74Trp (c.220A>T)?

AlphaMissense predicts likely benign (score 0.104) — an in-silico prediction, not a clinical call.

CHD6 p.Arg74Trp

c.220A>T · rs2044739902 · VCV2274824

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.104 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.104	likely benign
REVEL	0.488	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 38 kb · p 0.49 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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: CHD6
Protein: p.Arg74Trp
Coding: c.220A>T
MANE Select: NM_032221
dbSNP: rs2044739902
Type: single nucleotide variant
Location: chr20:41533384 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 (gnomAD)
Residue 74: the 'required for dna-dependent atpase activity' region; the 'disordered' region

Full CHD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD6 c.1858-19G>A Benign ★★ same type
CHD6 c.554+5G>A Benign/Likely benign ★★ same type
CHD6 c.852+4T>C Benign ★★ same type
CHD6 p.Ala1205Gly Benign ★★ same type
CHD6 p.Arg2389Cys Benign ★★ same type
CHD6 p.Glu1271= Benign ★★ same type
CHD6 p.Glu2404Gln Benign ★★ same type
CHD6 p.Gly1519Asp Benign ★★ 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/chd6-p-arg74trp (accessed [today's date]).

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