Is CHRND p.Leu331= (c.993C>T) pathogenic?

CHRND p.Leu331= (c.993C>T) is classified Likely benign in CHRND (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-22). Very rare (popmax 0.000424%, nfe); Associated with lethal multiple pterygium syndrome.

What condition is associated with CHRND p.Leu331= (c.993C>T)?

CHRND p.Leu331= (c.993C>T) is associated with lethal multiple pterygium syndrome (ClinVar).

How common is CHRND p.Leu331= (c.993C>T) in the general population?

CHRND p.Leu331= (c.993C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

CHRND p.Leu331=

c.993C>T · rs760991691 · VCV2891359

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

lethal multiple pterygium syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.036	GERP -1.2, phastCons 0.86
Overall
CADD	8.721	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,054 alleles

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

Overall 0.00031% 5/1,613,882 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.Leu331=
Coding: c.993C>T
MANE Select: NM_000751
dbSNP: rs760991691
Type: single nucleotide variant
Location: chr2:232531602 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB
Residue 331: an α-helix

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.Leu331Phe Uncertain significance ★ ⚠ same residue
CHRND p.Leu331Val 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

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-leu331 (accessed [today's date]).

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