Is CHRNG p.Ser372Phe (c.1115C>T) pathogenic?

CHRNG p.Ser372Phe (c.1115C>T) is classified Conflicting classifications of pathogenicity in CHRNG (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0876); Rare (popmax 0.324%, nfe); Associated with autosomal recessive multiple pterygium syndrome.

How common is CHRNG p.Ser372Phe (c.1115C>T) in the general population?

CHRNG p.Ser372Phe (c.1115C>T) is rare (popmax 0.324%, nfe) (gnomAD).

What do computational predictors say about CHRNG p.Ser372Phe (c.1115C>T)?

AlphaMissense predicts likely benign (score 0.0876) — an in-silico prediction, not a clinical call.

CHRNG p.Ser372Phe

Q: What condition is associated with CHRNG p.Ser372Phe (c.1115C>T)?

CHRNG p.Ser372Phe (c.1115C>T) is associated with autosomal recessive multiple pterygium syndrome, lethal multiple pterygium syndrome (ClinVar).

c.1115C>T · rs145433186 · VCV235269

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0876 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.324%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive multiple pterygium syndrome

Computational evidence

Protein change
AlphaMissense	0.0876	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -8.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.2	GERP 0.66
Regional constraint	o/e 0.94	unconstrained · MANE · 5,965 bp · p 0.099 · regional, not allelic
Overall
CADD	13.76	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 0.324% European (non-Finnish) · 3,828/1,180,022 alleles

Filtering AF 0.316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.312%

Overall 0.257% 4,145/1,613,742 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.324%	308
Remaining individualsnot grpmax-eligible	0.222%	450
South Asian	0.079%	1,265
Admixed American	0.0766%	1,305
African / African-American	0.0493%	2,029
Finnishnot grpmax-eligible	0.033%	3,028
Middle Eastern	0.0165%	6,060
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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.Ser372Phe
Coding: c.1115C>T
MANE Select: NM_145702 · reported on NM_005199
dbSNP: rs145433186
Type: single nucleotide variant
Location: chr2:232544446 (GRCh38)

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

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-ser372phe (accessed [today's date]).

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