Is CHRNG p.Pro134fs (c.401_402del) pathogenic?

CHRNG p.Pro134fs (c.401402del) is classified Pathogenic in CHRNG (ClinVar, Multiple submitters, 10 submitters; last evaluated 2024-02-26). Ultra-rare (popmax 0.0103%, nfe); Associated with CHRNG-related disorder.

What condition is associated with CHRNG p.Pro134fs (c.401_402del)?

CHRNG p.Pro134fs (c.401_402del) is associated with CHRNG-related disorder, lethal multiple pterygium syndrome, autosomal recessive multiple pterygium syndrome (ClinVar).

How common is CHRNG p.Pro134fs (c.401_402del) in the general population?

CHRNG p.Pro134fs (c.401_402del) is ultra-rare (popmax 0.0103%, nfe) (gnomAD).

CHRNG p.Pro134fs

c.401_402del · rs747067203 · VCV419026

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, nfe)

Conditions

CHRNG-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP -2.8, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0103% European (non-Finnish) · 121/1,180,004 alleles

Filtering AF 0.00876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0082%

Overall 0.00905% 146/1,614,004 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0112%	8,926
European (non-Finnish)grpmax	0.0103%	9,752
Admixed American	0.01%	10,001
African / African-American	0.00801%	12,484
East Asian	0.00446%	22,438
South Asian	0.00439%	22,772

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro134fs
Coding: c.401_402del
MANE Select: NM_005199
dbSNP: rs747067203
Type: Deletion
Location: chr2:232541424 (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

CHRNG-related disorder

Also linked: lethal multiple pterygium syndrome autosomal recessive multiple pterygium syndrome

Similar variants

CHRNG c.240+1del Pathogenic/Likely pathogenic ★★ same condition
CHRNG p.Arg452fs Pathogenic/Likely pathogenic ★★ same condition
CHRNG p.Arg46fs Pathogenic/Likely pathogenic ★★ same condition
CHRNG p.Asp135fs Pathogenic/Likely pathogenic ★★ same condition
CHRNG p.Glu177_Ile178insTer Pathogenic/Likely pathogenic ★★ same condition
CHRNG p.Pro361fs Pathogenic/Likely pathogenic ★★ same condition
CHRNG p.Val253fs Pathogenic ★★ same condition
CHRNG c.921-68del Benign ★★ 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-pro134fs (accessed [today's date]).

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