Is CHD5 p.Phe484Leu (c.1452C>G) pathogenic?

CHD5 p.Phe484Leu (c.1452C>G) is classified Uncertain significance in CHD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: ambiguous (0.383); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CHD5 p.Phe484Leu (c.1452C>G)?

CHD5 p.Phe484Leu (c.1452C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CHD5 p.Phe484Leu (c.1452C>G) in the general population?

CHD5 p.Phe484Leu (c.1452C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD5 p.Phe484Leu (c.1452C>G)?

AlphaMissense predicts ambiguous (score 0.383) — an in-silico prediction, not a clinical call.

CHD5 p.Phe484Leu

c.1452C>G · VCV4002131

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.383 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.383	ambiguous
REVEL	0.239	benign-leaning
SaProt	LLR -3.27	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -2.2, phastCons 0.97
Overall
CADD	16.5	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.Phe484Leu
Coding: c.1452C>G
MANE Select: NM_004627 · reported on NM_015557
Type: single nucleotide variant
Location: chr1:6146803 (GRCh38)
Structure: AlphaFold pLDDT 78.15 · 4 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD5 p.Ala1435Thr Uncertain significance ★★ ⚠ same condition
CHD5 p.Ala1446Ser Uncertain significance ★★ ⚠ same condition
CHD5 p.Ala215Val Uncertain significance ★★ same condition
CHD5 p.Arg1337Cys Uncertain significance ★★ same condition
CHD5 p.Asn21Ser Uncertain significance ★★ ⚠ same condition
CHD5 p.Asp414Asn Uncertain significance ★★ same condition
CHD5 p.Gln979His Uncertain significance ★★ ⚠ same condition
CHD5 p.Glu1302Val 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-phe484leu (accessed [today's date]).

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