Is CHD6 p.Pro73Arg (c.218C>G) pathogenic?

CHD6 p.Pro73Arg (c.218C>G) is classified Uncertain significance in CHD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-24). AlphaMissense: likely benign (0.0949); Ultra-rare (popmax 0.02%, afr).

How common is CHD6 p.Pro73Arg (c.218C>G) in the general population?

CHD6 p.Pro73Arg (c.218C>G) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about CHD6 p.Pro73Arg (c.218C>G)?

AlphaMissense predicts likely benign (score 0.0949) — an in-silico prediction, not a clinical call.

CHD6 p.Pro73Arg

c.218C>G · rs367761164 · VCV2517140

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0949 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Computational evidence

Protein change
AlphaMissense	0.0949	likely benign
REVEL	0.304	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 38 kb · p 0.49 · regional, not allelic
Overall
CADD	21.9	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

Grpmax group 0.02% African / African-American · 15/74,840 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0099%

Overall 0.00136% 22/1,613,776 alleles · ultra-rare exomes 15/1,461,832 · genomes 7/151,944 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	4,989
Remaining individualsnot grpmax-eligible	0.008%	12,496
South Asian	0.0022%	45,534

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: CHD6
Protein: p.Pro73Arg
Coding: c.218C>G
MANE Select: NM_032221
dbSNP: rs367761164
Type: single nucleotide variant
Location: chr20:41533386 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 (gnomAD)
Residue 73: 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-pro73arg (accessed [today's date]).

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