Is CHD1 p.Pro1423Ser (c.4267C>T) pathogenic?

CHD1 p.Pro1423Ser (c.4267C>T) is classified Uncertain significance in CHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely pathogenic (0.998); Absent from gnomAD v4.1.

How common is CHD1 p.Pro1423Ser (c.4267C>T) in the general population?

CHD1 p.Pro1423Ser (c.4267C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD1 p.Pro1423Ser (c.4267C>T)?

AlphaMissense predicts likely pathogenic (score 0.998) — an in-silico prediction, not a clinical call.

CHD1 p.Pro1423Ser

c.4267C>T · VCV3764358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.998	likely pathogenic · top 7% in CHD1
REVEL	0.781	moderately pathogenic-leaning
SaProt	LLR -9.59	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
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 0.35	constrained · MANE · 5,084 bp · p 1.3e-07 · regional, not allelic
Overall
CADD	26.5	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.Pro1423Ser
Coding: c.4267C>T
MANE Select: NM_001270
Type: single nucleotide variant
Location: chr5:98863568 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.63 · 18 PDB
Residue 1423: the 'chd1 helical c-terminal domain (chct)' region

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-pro1423ser (accessed [today's date]).

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