Is CHD1 p.Phe463Ser (c.1388T>C) pathogenic?

CHD1 p.Phe463Ser (c.1388T>C) is classified Uncertain significance in CHD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-01). AlphaMissense: likely pathogenic (0.9979); Absent from gnomAD v4.1; Associated with CHD1-related disorder.

What condition is associated with CHD1 p.Phe463Ser (c.1388T>C)?

CHD1 p.Phe463Ser (c.1388T>C) is associated with CHD1-related disorder (ClinVar).

How common is CHD1 p.Phe463Ser (c.1388T>C) in the general population?

CHD1 p.Phe463Ser (c.1388T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD1 p.Phe463Ser (c.1388T>C)?

AlphaMissense predicts likely pathogenic (score 0.9979) — an in-silico prediction, not a clinical call.

CHD1 p.Phe463Ser

c.1388T>C · rs2479681935 · VCV3033802

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9979 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CHD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9979	likely pathogenic · top 7% in CHD1
REVEL	0.779	moderately pathogenic-leaning
SaProt	LLR -10.37	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,200 bp · p 0.24 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Phe463Ser
Coding: c.1388T>C
MANE Select: NM_001270
dbSNP: rs2479681935
Type: single nucleotide variant
Location: chr5:98897298 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.63 · 18 PDB
Residue 463: 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.Pro768Ser 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-phe463ser (accessed [today's date]).

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