Is CHD3 p.Val1293Met (c.3877G>A) pathogenic?

CHD3 p.Val1293Met (c.3877G>A) is classified Conflicting classifications of pathogenicity in CHD3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-30). AlphaMissense: likely pathogenic (0.8444); Absent from gnomAD v4.1; Associated with Snijders Blok-Campeau syndrome.

What condition is associated with CHD3 p.Val1293Met (c.3877G>A)?

CHD3 p.Val1293Met (c.3877G>A) is associated with Snijders Blok-Campeau syndrome (ClinVar).

How common is CHD3 p.Val1293Met (c.3877G>A) in the general population?

CHD3 p.Val1293Met (c.3877G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD3 p.Val1293Met (c.3877G>A)?

AlphaMissense predicts likely pathogenic (score 0.8444) — an in-silico prediction, not a clinical call.

CHD3 p.Val1293Met

c.3877G>A · rs2545018939 · VCV2576575

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8444 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Snijders Blok-Campeau syndrome

Computational evidence

Protein change
AlphaMissense	0.8444	likely pathogenic
REVEL	0.686	pathogenic-leaning
SaProt	LLR -7.64	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 1.9, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 3,550 bp · p 4.9e-38 · regional, not allelic
Overall
CADD	32.0	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: CHD3
Protein: p.Val1293Met
Coding: c.3877G>A
MANE Select: NM_001005273
dbSNP: rs2545018939
Type: single nucleotide variant
Location: chr17:7903974 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 1293: 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 p.Val1293Ala Likely pathogenic ★ same residue
CHD3 p.Val1293Leu Uncertain significance ★ ⚠ same residue
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

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-val1293met (accessed [today's date]).

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