Is CHRND p.Arg413Ser (c.1237C>A) pathogenic?

CHRND p.Arg413Ser (c.1237C>A) is classified Uncertain significance in CHRND (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-02). AlphaMissense: ambiguous (0.4727); Very rare (popmax 8.47e-05%, nfe); Associated with lethal multiple pterygium syndrome.

What condition is associated with CHRND p.Arg413Ser (c.1237C>A)?

CHRND p.Arg413Ser (c.1237C>A) is associated with lethal multiple pterygium syndrome (ClinVar).

How common is CHRND p.Arg413Ser (c.1237C>A) in the general population?

CHRND p.Arg413Ser (c.1237C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CHRND p.Arg413Ser (c.1237C>A)?

AlphaMissense predicts ambiguous (score 0.4727) — an in-silico prediction, not a clinical call.

CHRND p.Arg413Ser

c.1237C>A · rs1242056715 · VCV534531

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4727 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

lethal multiple pterygium syndrome

Computational evidence

Protein change
AlphaMissense	0.4727	ambiguous
REVEL	0.466	indeterminate
SaProt	LLR -5.61	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.97 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 9,093 bp · p 0.12 · regional, not allelic
Overall
CADD	23.3	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 8.47e-05% European (non-Finnish) · 1/1,180,032 alleles

Overall 6.84e-05% 1/1,461,750 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.Arg413Ser
Coding: c.1237C>A
MANE Select: NM_000751
dbSNP: rs1242056715
Type: single nucleotide variant
Location: chr2:232534120 (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 p.Arg413Cys Uncertain significance ★★ ⚠ same residue
CHRND p.Arg413His Uncertain significance ★ ⚠ same residue
CHRND p.Arg413Leu Uncertain significance ★ ⚠ same residue
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

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-arg413ser (accessed [today's date]).

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