Is CHRND p.Cys129Arg (c.385T>C) pathogenic?

CHRND p.Cys129Arg (c.385T>C) is classified Uncertain significance in CHRND (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-19). AlphaMissense: likely pathogenic (0.952); Very rare (popmax 0.000424%, nfe); Associated with lethal multiple pterygium syndrome.

What condition is associated with CHRND p.Cys129Arg (c.385T>C)?

CHRND p.Cys129Arg (c.385T>C) is associated with lethal multiple pterygium syndrome (ClinVar).

How common is CHRND p.Cys129Arg (c.385T>C) in the general population?

CHRND p.Cys129Arg (c.385T>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about CHRND p.Cys129Arg (c.385T>C)?

AlphaMissense predicts likely pathogenic (score 0.952) — an in-silico prediction, not a clinical call.

CHRND p.Cys129Arg

c.385T>C · rs2469718968 · VCV3011044

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.952 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

lethal multiple pterygium syndrome

Computational evidence

Protein change
AlphaMissense	0.952	likely pathogenic · top 9% in CHRND
REVEL	0.774	moderately pathogenic-leaning
SaProt	LLR -12.66	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 4.1	GERP 1.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 9,093 bp · p 0.12 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,030 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,880 alleles · very rare

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: CHRND
Protein: p.Cys129Arg
Coding: c.385T>C
MANE Select: NM_000751
dbSNP: rs2469718968
Type: single nucleotide variant
Location: chr2:232528532 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB

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

Disease context

lethal multiple pterygium syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHRND c.1252+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHRND c.821-2A>C Pathogenic/Likely pathogenic ★★ same condition
CHRND c.933-2A>G Likely pathogenic ★★ same condition
CHRND p.Arg336Gln Likely pathogenic ★★ same condition
CHRND p.Arg43Trp Pathogenic/Likely pathogenic ★★ same condition
CHRND p.Cys257Arg Pathogenic/Likely pathogenic ★★ same condition
CHRND p.Trp78Ter Pathogenic ★★ same condition
CHRND p.Trp83Ter Pathogenic/Likely pathogenic ★★ 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/chrnd-p-cys129arg (accessed [today's date]).

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