Is CHD5 p.Leu47Phe (c.139C>T) pathogenic?

CHD5 p.Leu47Phe (c.139C>T) is classified Likely pathogenic in CHD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: likely benign (0.0694); Very rare (popmax 0.00167%, amr); Associated with parenti-mignot neurodevelopmental syndrome.

What condition is associated with CHD5 p.Leu47Phe (c.139C>T)?

CHD5 p.Leu47Phe (c.139C>T) is associated with parenti-mignot neurodevelopmental syndrome (ClinVar).

How common is CHD5 p.Leu47Phe (c.139C>T) in the general population?

CHD5 p.Leu47Phe (c.139C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CHD5 p.Leu47Phe (c.139C>T)?

AlphaMissense predicts likely benign (score 0.0694) — an in-silico prediction, not a clinical call.

CHD5 p.Leu47Phe

c.139C>T · VCV3375462

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0694 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

parenti-mignot neurodevelopmental syndrome

Computational evidence

Protein change
AlphaMissense	0.0694	likely benign ⚠ discordant with ClinVar
REVEL	0.262	benign-leaning
SaProt	LLR -7.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Overall
CADD	26.0	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 0.00167% Admixed American · 1/59,970 alleles

Overall 0.000137% 2/1,459,720 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,970
Remaining individualsnot grpmax-eligible	0.0016%	62,406

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: CHD5
Protein: p.Leu47Phe
Coding: c.139C>T
MANE Select: NM_004627 · reported on NM_015557
Type: single nucleotide variant
Location: chr1:6168218 (GRCh38)
Structure: AlphaFold pLDDT 78.15 · 4 PDB
Residue 47: an α-helix; the 'interaction with get3/trc40' region

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-leu47phe (accessed [today's date]).

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