Is CORIN p.Cys830Ser (c.2489G>C) pathogenic?

CORIN p.Cys830Ser (c.2489G>C) is classified Uncertain significance in CORIN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-18). AlphaMissense: likely pathogenic (0.8945); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CORIN p.Cys830Ser (c.2489G>C)?

CORIN p.Cys830Ser (c.2489G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CORIN p.Cys830Ser (c.2489G>C) in the general population?

CORIN p.Cys830Ser (c.2489G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CORIN p.Cys830Ser (c.2489G>C)?

AlphaMissense predicts likely pathogenic (score 0.8945) — an in-silico prediction, not a clinical call.

CORIN p.Cys830Ser

c.2489G>C · rs1436374067 · VCV2537594

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8945 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8945	likely pathogenic
REVEL	0.292	indeterminate
SaProt	LLR -9.54	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 242 kb · p 0.14 · regional, not allelic
Overall
CADD	27.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CORIN
Protein: p.Cys830Ser
Coding: c.2489G>C
MANE Select: NM_006587
dbSNP: rs1436374067
Type: single nucleotide variant
Location: chr4:47623622 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.20
Residue 830: the peptidase s1 domain

Full CORIN 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

CORIN p.Ser542Thr Uncertain significance ★★ ⚠ same condition
CORIN p.Val361Met Uncertain significance ★★ ⚠ same condition
LRP4 p.Ala1661Thr Uncertain significance ★★ ⚠ same condition
LRP4 p.Ala1727Thr Uncertain significance ★★ ⚠ same condition
LRP4 p.Arg1194Trp Uncertain significance ★★ ⚠ same condition
LRP4 p.Arg1425Gln Uncertain significance ★★ ⚠ same condition
LRP4 p.Arg1506Trp Uncertain significance ★★ ⚠ same condition
LRP4 p.Arg202His 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/corin-p-cys830ser (accessed [today's date]).

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