Is CHRND p.Lys67= (c.201A>G) pathogenic?

CHRND p.Lys67= (c.201A>G) is classified Uncertain significance in CHRND (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-31). Very rare (popmax 0.00223%, eas); Associated with lethal multiple pterygium syndrome.

What condition is associated with CHRND p.Lys67= (c.201A>G)?

CHRND p.Lys67= (c.201A>G) is associated with lethal multiple pterygium syndrome (ClinVar).

How common is CHRND p.Lys67= (c.201A>G) in the general population?

CHRND p.Lys67= (c.201A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

CHRND p.Lys67=

c.201A>G · VCV3621135

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

lethal multiple pterygium syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	acceptor loss, 2 bp away · masked 0 · deltas
Pangolin	Δ0.21	loss · gain 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.5	GERP -0.49, phastCons 1
Overall
CADD	13.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,856 alleles

Overall 0.000124% 2/1,612,858 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,856
European (non-Finnish)	8.48e-05%	1,179,021

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.Lys67=
Coding: c.201A>G
MANE Select: NM_000751
Type: single nucleotide variant
Location: chr2:232527403 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB
Residue 67: a β-strand

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-lys67 (accessed [today's date]).

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