Is CHD1 p.Pro768Ser (c.2302C>T) pathogenic?

CHD1 p.Pro768Ser (c.2302C>T) is classified Uncertain significance in CHD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-22). AlphaMissense: likely benign (0.2746); Absent from gnomAD v4.1; Associated with CHD1-related disorder.

What condition is associated with CHD1 p.Pro768Ser (c.2302C>T)?

CHD1 p.Pro768Ser (c.2302C>T) is associated with CHD1-related disorder (ClinVar).

How common is CHD1 p.Pro768Ser (c.2302C>T) in the general population?

CHD1 p.Pro768Ser (c.2302C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD1 p.Pro768Ser (c.2302C>T)?

AlphaMissense predicts likely benign (score 0.2746) — an in-silico prediction, not a clinical call.

CHD1 p.Pro768Ser

c.2302C>T · rs1210210931 · VCV3059935

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2746 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CHD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.2746	likely benign
REVEL	0.44	indeterminate
SaProt	LLR -10.29	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 4,350 bp · p 0.00075 · regional, not allelic
Overall
CADD	25.0	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

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: CHD1
Protein: p.Pro768Ser
Coding: c.2302C>T
MANE Select: NM_001270
dbSNP: rs1210210931
Type: single nucleotide variant
Location: chr5:98889117 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.63 · 18 PDB
Residue 768: an α-helix

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

Disease context

CHD1-related disorder

Similar variants

CHD1 c.4577-7C>A Uncertain significance ★ same condition
CHD1 p.Arg833Ser Uncertain significance ★ ⚠ same condition
CHD1 p.His476Tyr Uncertain significance ★ ⚠ same condition
CHD1 p.Arg1112Cys Uncertain significance ⚠ same condition
CHD1 p.Arg1541Ser Uncertain significance ⚠ same condition
CHD1 p.Asn1083Asp Uncertain significance ⚠ same condition
CHD1 p.Asp1564Glu Uncertain significance ⚠ same condition
CHD1 p.Phe463Ser Uncertain significance ⚠ same condition

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-pro768ser (accessed [today's date]).

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