Is CHD6 p.Pro563Ala (c.1687C>G) pathogenic?

CHD6 p.Pro563Ala (c.1687C>G) is classified Uncertain significance in CHD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely benign (0.0591); Absent from gnomAD v4.1; Associated with CHD6-related disorder.

What condition is associated with CHD6 p.Pro563Ala (c.1687C>G)?

CHD6 p.Pro563Ala (c.1687C>G) is associated with CHD6-related disorder (ClinVar).

How common is CHD6 p.Pro563Ala (c.1687C>G) in the general population?

CHD6 p.Pro563Ala (c.1687C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD6 p.Pro563Ala (c.1687C>G)?

AlphaMissense predicts likely benign (score 0.0591) — an in-silico prediction, not a clinical call.

CHD6 p.Pro563Ala

c.1687C>G · VCV4854499

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0591 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

CHD6-related disorder

Computational evidence

Protein change
AlphaMissense	0.0591	likely benign
REVEL	0.323	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.27	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 57 kb · p 1.4e-47 · regional, not allelic
Overall
CADD	23.8	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.Pro563Ala
Coding: c.1687C>G
MANE Select: NM_032221
Type: single nucleotide variant
Location: chr20:41488598 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 (gnomAD)
Residue 563: the helicase atp-binding domain; the 'required for dna-dependent atpase activity' region

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

Disease context

CHD6-related disorder

Similar variants

CHD6 p.Arg1595Gly Uncertain significance ★ ⚠ same condition
CHD6 p.Lys1590Asn Uncertain significance ★ same condition
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

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-pro563ala (accessed [today's date]).

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