Is CHRNG p.Pro142= (c.426G>A) pathogenic?

CHRNG p.Pro142= (c.426G>A) is classified Conflicting classifications of pathogenicity in CHRNG (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-03-01). Ultra-rare (popmax 0.0339%, nfe); Associated with lethal multiple pterygium syndrome.

What condition is associated with CHRNG p.Pro142= (c.426G>A)?

CHRNG p.Pro142= (c.426G>A) is associated with lethal multiple pterygium syndrome, autosomal recessive multiple pterygium syndrome (ClinVar).

How common is CHRNG p.Pro142= (c.426G>A) in the general population?

CHRNG p.Pro142= (c.426G>A) is ultra-rare (popmax 0.0339%, nfe) (gnomAD).

CHRNG p.Pro142=

c.426G>A · rs375894671 · VCV896327

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0339%, 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 -13	GERP -4.3
Overall
CADD	0.779	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0339% European (non-Finnish) · 400/1,179,990 alleles

Filtering AF 0.0311% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.03%

Overall 0.0278% 448/1,614,104 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0339%	2,950
Remaining individualsnot grpmax-eligible	0.032%	3,125
East Asian	0.0267%	3,740
Admixed American	0.0133%	7,502
African / African-American	0.00533%	18,758
South Asian	0.00329%	30,362
Finnishnot grpmax-eligible	0.00156%	64,026

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: CHRNG
Protein: p.Pro142=
Coding: c.426G>A
MANE Select: NM_005199
dbSNP: rs375894671
Type: single nucleotide variant
Location: chr2:232541449 (GRCh38)
Gene constraint: LOEUF 1.286 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.91

Full CHRNG 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: autosomal recessive multiple pterygium syndrome

Similar variants

CHRNG c.1380+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHRNG c.350+2T>C Pathogenic/Likely pathogenic ★★ same condition
CHRNG c.351-2A>G Likely pathogenic ★★ same condition
CHRNG c.56-1G>A Pathogenic ★★ same condition
CHRNG c.805+1G>A Likely pathogenic ★★ same condition
CHRNG p.Arg239Cys Pathogenic ★★ same condition
CHRNG p.Arg46Ter Pathogenic ★★ same condition
CHRNG p.Arg68Ter 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/chrng-p-pro142 (accessed [today's date]).

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