Is CHD1 p.Ile565Val (c.1693A>G) pathogenic?

CHD1 p.Ile565Val (c.1693A>G) is classified Uncertain significance in CHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.072); Very rare (popmax 8.48e-05%, nfe).

How common is CHD1 p.Ile565Val (c.1693A>G) in the general population?

CHD1 p.Ile565Val (c.1693A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CHD1 p.Ile565Val (c.1693A>G)?

AlphaMissense predicts likely benign (score 0.072) — an in-silico prediction, not a clinical call.

CHD1 p.Ile565Val

c.1693A>G · VCV4653252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.072 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.072	likely benign
REVEL	0.265	benign-leaning
SaProt	LLR -5.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.69, phastCons 1
Regional constraint	o/e 0.36	unconstrained · MANE · 2,627 bp · p 1e-13 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,274 alleles

Overall 6.2e-05% 1/1,613,332 alleles · very rare exomes 1/1,461,006 · genomes 0/152,326 · joint denominator

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: CHD1
Protein: p.Ile565Val
Coding: c.1693A>G
MANE Select: NM_001270
Type: single nucleotide variant
Location: chr5:98896243 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.63 · 18 PDB
Residue 565: the helicase atp-binding domain; an α-helix

Full CHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD1 p.Arg1378Gly Uncertain significance ★★ ⚠ same type
CHD1 p.Arg1659Thr Uncertain significance ★★ ⚠ same type
CHD1 p.Arg1676Gly Uncertain significance ★★ ⚠ same type
CHD1 p.Arg1708Gln Uncertain significance ★★ same type
CHD1 p.Arg1708Trp Uncertain significance ★★ ⚠ same type
CHD1 p.Arg233His Uncertain significance ★★ same type
CHD1 p.Arg70Ter Uncertain significance ★★ same type
CHD1 p.Asn1518His Uncertain significance ★★ ⚠ 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/chd1-p-ile565val (accessed [today's date]).

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