Is CHRND p.Ala15= (c.45G>A) pathogenic?

CHRND p.Ala15= (c.45G>A) is classified Conflicting classifications of pathogenicity in CHRND (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-27). Rare (popmax 0.177%, mid); Associated with lethal multiple pterygium syndrome.

What condition is associated with CHRND p.Ala15= (c.45G>A)?

CHRND p.Ala15= (c.45G>A) is associated with lethal multiple pterygium syndrome, congenital myasthenic syndrome (ClinVar).

How common is CHRND p.Ala15= (c.45G>A) in the general population?

CHRND p.Ala15= (c.45G>A) is rare (popmax 0.177%, mid) (gnomAD).

CHRND p.Ala15=

c.45G>A · rs138609765 · VCV466194

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.177%, mid)

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 -7.5	GERP -3.4
Overall
CADD	0.862	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.177% Middle Eastern · 10/5,662 alleles

Filtering AF 0.0958% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0729%

Overall 0.0227% 366/1,612,900 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.177%	566
Admixed American	0.0834%	1,199
Remaining individualsnot grpmax-eligible	0.0417%	2,400
South Asian	0.0275%	3,639
Ashkenazi Jewishnot grpmax-eligible	0.0271%	3,694
European (non-Finnish)	0.0205%	4,875
Finnishnot grpmax-eligible	0.00313%	31,923
African / African-American	0.00267%	37,502
East Asian	0.00223%	44,842

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.Ala15=
Coding: c.45G>A
MANE Select: NM_000751
dbSNP: rs138609765
Type: single nucleotide variant
Location: chr2:232526260 (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

Also linked: congenital myasthenic syndrome

Similar variants

CHRND p.Ala15Val Conflicting classifications of pathogenicity ★ ⚠ 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-ala15 (accessed [today's date]).

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