Is CHRNG p.Asp119= (c.357C>T) pathogenic?

CHRNG p.Asp119= (c.357C>T) is classified Conflicting classifications of pathogenicity in CHRNG (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-31). Ultra-rare (popmax 0.0134%, eas); Associated with lethal multiple pterygium syndrome.

What condition is associated with CHRNG p.Asp119= (c.357C>T)?

CHRNG p.Asp119= (c.357C>T) is associated with lethal multiple pterygium syndrome, autosomal recessive multiple pterygium syndrome (ClinVar).

How common is CHRNG p.Asp119= (c.357C>T) in the general population?

CHRNG p.Asp119= (c.357C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

CHRNG p.Asp119=

c.357C>T · rs749995118 · VCV335001

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 0.0134%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.7	GERP -1.4
Overall
CADD	10.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,880 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00161% 26/1,613,912 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,480
Admixed American	0.00333%	29,996
European (non-Finnish)	0.00136%	73,748
African / African-American	0.00134%	74,882
South Asian	0.0011%	91,092

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.Asp119=
Coding: c.357C>T
MANE Select: NM_005199
dbSNP: rs749995118
Type: single nucleotide variant
Location: chr2:232541380 (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-asp119 (accessed [today's date]).

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