Is CHRND p.Cys151Ser (c.452G>C) pathogenic?

CHRND p.Cys151Ser (c.452G>C) is classified Likely pathogenic in CHRND (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-28). AlphaMissense: likely pathogenic (0.9963); Absent from gnomAD v4.1; Associated with arthrogryposis multiplex congenita.

What condition is associated with CHRND p.Cys151Ser (c.452G>C)?

CHRND p.Cys151Ser (c.452G>C) is associated with arthrogryposis multiplex congenita, fetal akinesia deformation sequence 1 (ClinVar).

How common is CHRND p.Cys151Ser (c.452G>C) in the general population?

CHRND p.Cys151Ser (c.452G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHRND p.Cys151Ser (c.452G>C)?

AlphaMissense predicts likely pathogenic (score 0.9963) — an in-silico prediction, not a clinical call.

CHRND p.Cys151Ser

c.452G>C · rs1574630583 · VCV692273

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9963 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

arthrogryposis multiplex congenita

Computational evidence

Protein change
AlphaMissense	0.9963	likely pathogenic ✓ concordant with ClinVar · top 1% in CHRND
REVEL	0.955	strongly pathogenic-leaning
SaProt	LLR -12.30	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 9.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 9,093 bp · p 0.12 · regional, not allelic
Overall
CADD	27.7	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: CHRND
Protein: p.Cys151Ser
Coding: c.452G>C
MANE Select: NM_000751
dbSNP: rs1574630583
Type: single nucleotide variant
Location: chr2:232528599 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB
Residue 151: a disulfide bond

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

Disease context

arthrogryposis multiplex congenita — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: fetal akinesia deformation sequence 1

Similar variants

CHRND c.1252+1G>A Pathogenic/Likely pathogenic ★★ same type
CHRND c.821-2A>C Pathogenic/Likely pathogenic ★★ same type
CHRND c.933-2A>G Likely pathogenic ★★ same type
CHRND p.Arg336Gln Likely pathogenic ★★ same type
CHRND p.Arg43Trp Pathogenic/Likely pathogenic ★★ same type
CHRND p.Cys257Arg Pathogenic/Likely pathogenic ★★ same type
CHRND p.Trp78Ter Pathogenic ★★ same type
CHRND p.Trp83Ter Pathogenic/Likely pathogenic ★★ same type

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/chrnd-p-cys151ser (accessed [today's date]).

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