Is CHD6 p.Pro2630Ala (c.7888C>G) pathogenic?

CHD6 p.Pro2630Ala (c.7888C>G) is classified Uncertain significance in CHD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.1981); Very rare (popmax 0.00763%, nfe).

How common is CHD6 p.Pro2630Ala (c.7888C>G) in the general population?

CHD6 p.Pro2630Ala (c.7888C>G) is very rare (popmax 0.00763%, nfe) (gnomAD).

What do computational predictors say about CHD6 p.Pro2630Ala (c.7888C>G)?

AlphaMissense predicts likely benign (score 0.1981) — an in-silico prediction, not a clinical call.

CHD6 p.Pro2630Ala

c.7888C>G · rs575778947 · VCV3144188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1981 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00763%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1981	likely benign
REVEL	0.677	pathogenic-leaning
⇒ REVEL calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 616 bp · p 0.086 · regional, not allelic
Overall
CADD	24.8	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 0.00763% European (non-Finnish) · 90/1,180,016 alleles

Filtering AF 0.00631% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00584%

Overall 0.0057% 92/1,614,086 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00763%	13,111
Remaining individualsnot grpmax-eligible	0.0032%	31,253

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.Pro2630Ala
Coding: c.7888C>G
MANE Select: NM_032221
dbSNP: rs575778947
Type: single nucleotide variant
Location: chr20:41404853 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 (gnomAD)

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-pro2630ala (accessed [today's date]).

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