Is CHRNG p.Pro506Ser (c.1516C>T) pathogenic?

CHRNG p.Pro506Ser (c.1516C>T) is classified Benign/Likely benign in CHRNG (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0923); Low-frequency (popmax 1.08%, sas); Associated with lethal multiple pterygium syndrome.

What condition is associated with CHRNG p.Pro506Ser (c.1516C>T)?

CHRNG p.Pro506Ser (c.1516C>T) is associated with lethal multiple pterygium syndrome (ClinVar).

How common is CHRNG p.Pro506Ser (c.1516C>T) in the general population?

CHRNG p.Pro506Ser (c.1516C>T) is low-frequency (popmax 1.08%, sas) (gnomAD).

What do computational predictors say about CHRNG p.Pro506Ser (c.1516C>T)?

AlphaMissense predicts likely benign (score 0.0923) — an in-silico prediction, not a clinical call.

CHRNG p.Pro506Ser

c.1516C>T · rs71421651 · VCV235605

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0923 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.08%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

lethal multiple pterygium syndrome

Computational evidence

Protein change
AlphaMissense	0.0923	likely benign
REVEL	0.405	indeterminate
SaProt	LLR -9.23	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 5,965 bp · p 0.099 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.08% South Asian · 982/91,086 alleles

Filtering AF 1.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 1%

Overall 0.81% 13,082/1,614,182 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.08%	93
European (non-Finnish)	0.918%	109
Remaining individualsnot grpmax-eligible	0.742%	135
Middle Eastern	0.561%	178
Ashkenazi Jewishnot grpmax-eligible	0.554%	181
Finnishnot grpmax-eligible	0.514%	195
Admixed American	0.292%	343
African / African-American	0.129%	774

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.Pro506Ser
Coding: c.1516C>T
MANE Select: NM_005199
dbSNP: rs71421651
Type: single nucleotide variant
Location: chr2:232545678 (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

Similar variants

CHRNG p.Pro506= Likely benign ★ same residue
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

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-pro506ser (accessed [today's date]).

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