Is CHRNG p.Pro110= (c.330G>A) pathogenic?

CHRNG p.Pro110= (c.330G>A) is classified Conflicting classifications of pathogenicity in CHRNG (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-01-29). Very rare (popmax 0.008%, afr); Associated with autosomal recessive multiple pterygium syndrome.

How common is CHRNG p.Pro110= (c.330G>A) in the general population?

CHRNG p.Pro110= (c.330G>A) is very rare (popmax 0.008%, afr) (gnomAD).

CHRNG p.Pro110=

Q: What condition is associated with CHRNG p.Pro110= (c.330G>A)?

CHRNG p.Pro110= (c.330G>A) is associated with autosomal recessive multiple pterygium syndrome, lethal multiple pterygium syndrome (ClinVar).

c.330G>A · rs149931943 · VCV497740

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.008%, afr)

Conditions

autosomal recessive 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 -5.6	GERP -3
Overall
CADD	4.842	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.008% African / African-American · 6/75,016 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00149% 24/1,611,802 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.008%	12,503
Finnishnot grpmax-eligible	0.0064%	15,621
Admixed American	0.00334%	29,978
East Asian	0.00223%	44,816
South Asian	0.0022%	45,473
Remaining individualsnot grpmax-eligible	0.0016%	62,414
European (non-Finnish)	0.000678%	147,468

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.Pro110=
Coding: c.330G>A
MANE Select: NM_005199
dbSNP: rs149931943
Type: single nucleotide variant
Location: chr2:232540691 (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

autosomal recessive multiple pterygium syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lethal 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-pro110 (accessed [today's date]).

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