Is CHL1 p.Pro796Arg (c.2387C>G) pathogenic?

CHL1 p.Pro796Arg (c.2387C>G) is classified Uncertain significance in CHL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: ambiguous (0.4179); Very rare (popmax 0.00686%, nfe).

How common is CHL1 p.Pro796Arg (c.2387C>G) in the general population?

CHL1 p.Pro796Arg (c.2387C>G) is very rare (popmax 0.00686%, nfe) (gnomAD).

What do computational predictors say about CHL1 p.Pro796Arg (c.2387C>G)?

AlphaMissense predicts ambiguous (score 0.4179) — an in-silico prediction, not a clinical call.

CHL1 p.Pro796Arg

c.2387C>G · rs777362823 · VCV2396252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4179 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00686%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4179	ambiguous
REVEL	0.472	indeterminate
SaProt	LLR -13.74	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 86 kb · p 2e-21 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P780R vs ClinVar P796R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00686% European (non-Finnish) · 81/1,180,044 alleles

Filtering AF 0.00563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00527% 85/1,614,074 alleles · very rare exomes 77/1,461,884 · genomes 8/152,190 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00686%	14,568
Finnishnot grpmax-eligible	0.00468%	21,345
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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: CHL1
Protein: p.Pro796Arg
Coding: c.2387C>G
MANE Select: NM_006614
dbSNP: rs777362823
Type: single nucleotide variant
Location: chr3:389391 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.37
Residue 780 UniProt numbering: the fibronectin type-iii 2 domain

Full CHL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHL1 p.Pro796= Likely benign ★ same residue
CHL1 p.Ile100Val Uncertain significance ★★ ⚠ same type
CHL1 c.1306+10C>T Benign ★★ same type
CHL1 c.197+10G>C Benign ★★ same type
CHL1 p.Ala1105Val Likely benign ★★ same type
CHL1 p.Ala450= Likely benign ★★ same type
CHL1 p.Ala465= Benign ★★ same type
CHL1 p.Arg93= Benign/Likely benign ★★ same type

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/chl1-p-pro796arg (accessed [today's date]).

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