Is CHD3 p.Ala1259Val (c.3776C>T) pathogenic?

CHD3 p.Ala1259Val (c.3776C>T) is classified Likely pathogenic in CHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-20). AlphaMissense: likely pathogenic (0.8638); Absent from gnomAD v4.1; Associated with Snijders Blok-Campeau syndrome.

What condition is associated with CHD3 p.Ala1259Val (c.3776C>T)?

CHD3 p.Ala1259Val (c.3776C>T) is associated with Snijders Blok-Campeau syndrome (ClinVar).

How common is CHD3 p.Ala1259Val (c.3776C>T) in the general population?

CHD3 p.Ala1259Val (c.3776C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD3 p.Ala1259Val (c.3776C>T)?

AlphaMissense predicts likely pathogenic (score 0.8638) — an in-silico prediction, not a clinical call.

CHD3 p.Ala1259Val

c.3776C>T · rs2151608196 · VCV1330948

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8638 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Snijders Blok-Campeau syndrome

Computational evidence

Protein change
AlphaMissense	0.8638	likely pathogenic ✓ concordant with ClinVar
REVEL	0.854	moderately pathogenic-leaning
SaProt	LLR -12.28	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 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 3,550 bp · p 4.9e-38 · regional, not allelic
Overall
CADD	27.8	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: CHD3
Protein: p.Ala1259Val
Coding: c.3776C>T
MANE Select: NM_001005273
dbSNP: rs2151608196
Type: single nucleotide variant
Location: chr17:7903873 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 1259: a UniProt-annotated variant site (in snibcps)

Full CHD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Snijders Blok-Campeau syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD3 c.4073-2A>C Likely pathogenic ★★ same condition
CHD3 p.Arg1078Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1121Pro Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1169Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1169Pro Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1169Trp Pathogenic ★★ same condition
CHD3 p.Arg1172Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1172Trp Pathogenic/Likely pathogenic ★★ 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/chd3-p-ala1259val (accessed [today's date]).

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