Is CHRNG p.Pro7Leu (c.20C>T) pathogenic?

CHRNG p.Pro7Leu (c.20C>T) is classified Likely benign in CHRNG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-26). AlphaMissense: likely benign (0.0704); Ultra-rare (popmax 0.0134%, eas); Associated with Inborn genetic diseases.

What condition is associated with CHRNG p.Pro7Leu (c.20C>T)?

CHRNG p.Pro7Leu (c.20C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CHRNG p.Pro7Leu (c.20C>T) in the general population?

CHRNG p.Pro7Leu (c.20C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about CHRNG p.Pro7Leu (c.20C>T)?

AlphaMissense predicts likely benign (score 0.0704) — an in-silico prediction, not a clinical call.

CHRNG p.Pro7Leu

c.20C>T · rs200661257 · VCV3144688

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0704 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0704	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -6.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.8	GERP -3
Regional constraint	o/e 0.94	unconstrained · MANE · 5,965 bp · p 0.099 · regional, not allelic
Overall
CADD	0.008	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 0.0134% East Asian · 6/44,880 alleles

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

Overall 0.00211% 34/1,613,904 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,480
Admixed American	0.00666%	15,005
Remaining individualsnot grpmax-eligible	0.0064%	15,623
African / African-American	0.004%	25,010
Finnishnot grpmax-eligible	0.00313%	31,960
European (non-Finnish)	0.00127%	78,666

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.Pro7Leu
Coding: c.20C>T
MANE Select: NM_005199
dbSNP: rs200661257
Type: single nucleotide variant
Location: chr2:232539767 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHRNG p.Pro7= Likely benign ★ same residue
CHRNG p.Arg344Cys Uncertain significance ★★ ⚠ same condition
CHRNG p.Arg46Gln Uncertain significance ★★ ⚠ same condition
CHRNG p.Arg68Gln Uncertain significance ★★ ⚠ same condition
CHRNG p.Asn75Ser Uncertain significance ★★ ⚠ same condition
CHRNG p.Glu67Lys Uncertain significance ★★ ⚠ same condition
CHRNG p.His2Leu Uncertain significance ★★ ⚠ same condition
CHRNG p.Leu33Pro Uncertain significance ★★ ⚠ 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-pro7leu (accessed [today's date]).

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