Is CHRNG p.Pro43= (c.129C>T) pathogenic?

CHRNG p.Pro43= (c.129C>T) is classified Conflicting classifications of pathogenicity in CHRNG (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-03-30). Ultra-rare (popmax 0.0223%, eas); Associated with lethal multiple pterygium syndrome.

What condition is associated with CHRNG p.Pro43= (c.129C>T)?

CHRNG p.Pro43= (c.129C>T) is associated with lethal multiple pterygium syndrome, autosomal recessive multiple pterygium syndrome (ClinVar).

How common is CHRNG p.Pro43= (c.129C>T) in the general population?

CHRNG p.Pro43= (c.129C>T) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

CHRNG p.Pro43=

c.129C>T · rs151276788 · VCV334999

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Conditions

lethal multiple pterygium syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.2
Overall
CADD	0.061	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% East Asian · 10/44,890 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0158%

Overall 0.0158% 255/1,614,228 alleles · ultra-rare exomes 239/1,461,876 · genomes 16/152,352 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,489
Finnishnot grpmax-eligible	0.0219%	4,575
European (non-Finnish)	0.0186%	5,364
Remaining individualsnot grpmax-eligible	0.008%	12,501
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
African / African-American	0.00266%	37,531
South Asian	0.0022%	45,546
Admixed American	0.00167%	60,030

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.Pro43=
Coding: c.129C>T
MANE Select: NM_005199
dbSNP: rs151276788
Type: single nucleotide variant
Location: chr2:232540065 (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-pro43 (accessed [today's date]).

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