Is CHD5 p.Pro1124Ser (c.3370C>T) pathogenic?

CHD5 p.Pro1124Ser (c.3370C>T) is classified Likely pathogenic in CHD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-15). AlphaMissense: likely pathogenic (0.9925); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CHD5 p.Pro1124Ser (c.3370C>T)?

CHD5 p.Pro1124Ser (c.3370C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CHD5 p.Pro1124Ser (c.3370C>T) in the general population?

CHD5 p.Pro1124Ser (c.3370C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD5 p.Pro1124Ser (c.3370C>T)?

AlphaMissense predicts likely pathogenic (score 0.9925) — an in-silico prediction, not a clinical call.

CHD5 p.Pro1124Ser

c.3370C>T · VCV3832812

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9925 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9925	likely pathogenic ✓ concordant with ClinVar · top 4% in CHD5
REVEL	0.897	moderately pathogenic-leaning
SaProt	LLR -14.63	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.87, phastCons 1
Overall
CADD	33.0	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: CHD5
Protein: p.Pro1124Ser
Coding: c.3370C>T
MANE Select: NM_004627 · reported on NM_015557
Type: single nucleotide variant
Location: chr1:6130221 (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.Pro1124Leu Pathogenic/Likely pathogenic ★★ same residue
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

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-pro1124ser (accessed [today's date]).

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