Is CHD5 p.Val862Phe (c.2584G>T) pathogenic?

CHD5 p.Val862Phe (c.2584G>T) is classified Uncertain significance in CHD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-28). AlphaMissense: ambiguous (0.3898); Absent from gnomAD v4.1; Associated with parenti-mignot neurodevelopmental syndrome.

What condition is associated with CHD5 p.Val862Phe (c.2584G>T)?

CHD5 p.Val862Phe (c.2584G>T) is associated with parenti-mignot neurodevelopmental syndrome (ClinVar).

How common is CHD5 p.Val862Phe (c.2584G>T) in the general population?

CHD5 p.Val862Phe (c.2584G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD5 p.Val862Phe (c.2584G>T)?

AlphaMissense predicts ambiguous (score 0.3898) — an in-silico prediction, not a clinical call.

CHD5 p.Val862Phe

c.2584G>T · VCV3385378

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3898 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

parenti-mignot neurodevelopmental syndrome

Computational evidence

Protein change
AlphaMissense	0.3898	ambiguous
REVEL	0.66	pathogenic-leaning
SaProt	LLR -15.69	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Overall
CADD	29.2	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: CHD5
Protein: p.Val862Phe
Coding: c.2584G>T
MANE Select: NM_015557
Type: single nucleotide variant
Location: chr1:6136629 (GRCh38)
Structure: AlphaFold pLDDT 78.15 · 4 PDB

Full CHD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

parenti-mignot neurodevelopmental syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD5 c.4171+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD5 p.Arg193Trp Pathogenic/Likely pathogenic ★★ same condition
CHD5 c.79+5G>A Uncertain significance ★★ same condition
CHD5 p.Ala215Val Uncertain significance ★★ same condition
CHD5 p.Asp23Asn Uncertain significance ★★ ⚠ same condition
CHD5 p.Lys818Arg Uncertain significance ★★ ⚠ same condition
CHD5 p.Pro1215Leu Uncertain significance ★★ ⚠ same condition
CHD5 p.Pro1409Ser 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/chd5-p-val862phe (accessed [today's date]).

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