Is CHRND p.Arg87Trp (c.259C>T) pathogenic?

CHRND p.Arg87Trp (c.259C>T) is classified Uncertain significance in CHRND (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-17). AlphaMissense: likely pathogenic (0.7008); Very rare (popmax 0.00667%, afr); Associated with Inborn genetic diseases.

What condition is associated with CHRND p.Arg87Trp (c.259C>T)?

CHRND p.Arg87Trp (c.259C>T) is associated with Inborn genetic diseases, lethal multiple pterygium syndrome (ClinVar).

How common is CHRND p.Arg87Trp (c.259C>T) in the general population?

CHRND p.Arg87Trp (c.259C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about CHRND p.Arg87Trp (c.259C>T)?

AlphaMissense predicts likely pathogenic (score 0.7008) — an in-silico prediction, not a clinical call.

CHRND p.Arg87Trp

c.259C>T · rs375883569 · VCV1803670

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7008 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7008	likely pathogenic
REVEL	0.826	moderately pathogenic-leaning
SaProt	LLR -9.16	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.57, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 9,093 bp · p 0.12 · regional, not allelic
Overall
CADD	27.3	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 0.00667% African / African-American · 5/74,930 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00396%

Overall 0.00471% 76/1,614,046 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,986
European (non-Finnish)	0.00542%	18,438
Admixed American	0.00333%	30,000
South Asian	0.00329%	30,355
Remaining individualsnot grpmax-eligible	0.0032%	31,244

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.Arg87Trp
Coding: c.259C>T
MANE Select: NM_000751
dbSNP: rs375883569
Type: single nucleotide variant
Location: chr2:232528277 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB
Residue 87: an α-helix

Full CHRND 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

Also linked: lethal multiple pterygium syndrome

Similar variants

CHRND p.Arg87Gln 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
CHRND p.Cys257Arg Pathogenic/Likely pathogenic ★★ same condition
CHRND p.Trp78Ter 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-arg87trp (accessed [today's date]).

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