Is CHD3 p.Val1860Ile (c.5578G>A) pathogenic?

CHD3 p.Val1860Ile (c.5578G>A) is classified Uncertain significance in CHD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-13). AlphaMissense: likely pathogenic (0.6488); Very rare (popmax 0.00148%, nfe); Associated with Snijders Blok-Campeau syndrome.

What condition is associated with CHD3 p.Val1860Ile (c.5578G>A)?

CHD3 p.Val1860Ile (c.5578G>A) is associated with Snijders Blok-Campeau syndrome (ClinVar).

How common is CHD3 p.Val1860Ile (c.5578G>A) in the general population?

CHD3 p.Val1860Ile (c.5578G>A) is very rare (popmax 0.00148%, nfe) (gnomAD).

What do computational predictors say about CHD3 p.Val1860Ile (c.5578G>A)?

AlphaMissense predicts likely pathogenic (score 0.6488) — an in-silico prediction, not a clinical call.

CHD3 p.Val1860Ile

c.5578G>A · rs944136166 · VCV1711428

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6488 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00148%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Snijders Blok-Campeau syndrome

Computational evidence

Protein change
AlphaMissense	0.6488	likely pathogenic
REVEL	0.609	indeterminate
SaProt	LLR -6.45	tolerated
⇒ AlphaMissense calls this damaging; SaProt 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 1.9, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 1,771 bp · p 3.3e-13 · 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

Grpmax group 0.00148% European (non-Finnish) · 17/1,151,626 alleles

Filtering AF 0.000899% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000735%

Overall 0.00121% 17/1,404,186 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CHD3
Protein: p.Val1860Ile
Coding: c.5578G>A
MANE Select: NM_001005273
dbSNP: rs944136166
Type: single nucleotide variant
Location: chr17:7909326 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 1860: the 'required for interaction with pcnt' region; 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-val1860ile (accessed [today's date]).

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