Is CORIN p.Ser669fs (c.2004_2005del) pathogenic?

CORIN p.Ser669fs (c.20042005del) is classified Likely pathogenic in CORIN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-09). Ultra-rare (popmax 0.0286%, sas); Associated with cardiomyopathy, familial hypertrophic, 30, atrial.

What condition is associated with CORIN p.Ser669fs (c.2004_2005del)?

CORIN p.Ser669fs (c.2004_2005del) is associated with cardiomyopathy, familial hypertrophic, 30, atrial (ClinVar).

How common is CORIN p.Ser669fs (c.2004_2005del) in the general population?

CORIN p.Ser669fs (c.2004_2005del) is ultra-rare (popmax 0.0286%, sas) (gnomAD).

CORIN p.Ser669fs

c.2004_2005del · VCV3767951

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0286%, sas)

Conditions

cardiomyopathy, familial hypertrophic, 30, atrial

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.2	phastCons 0.98

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0286% South Asian · 26/91,032 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.0018% 29/1,613,952 alleles · ultra-rare exomes 29/1,461,664 · genomes 0/152,288 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0286%	3,501
Remaining individualsnot grpmax-eligible	0.0016%	62,500
European (non-Finnish)	0.00017%	589,967

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: CORIN
Protein: p.Ser669fs
Coding: c.2004_2005del
MANE Select: NM_006587
Type: Microsatellite
Location: chr4:47643209 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.20
Residue 669: the ldl-receptor class a 7 domain

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

Disease context

cardiomyopathy, familial hypertrophic, 30, atrial — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CORIN p.Met229fs Pathogenic ★ same condition
LRP4 p.Lys1794fs Uncertain significance ★★ same type
LRP4 p.Lys1806del Uncertain significance ★★ same type
LRP4 c.200-26TTTTC[2] Likely benign ★★ same type
LRP4 c.2814+13_2814+35del Benign/Likely benign ★★ same type
LRP4 c.923-8CT[2] Uncertain significance ★ same type
LRP4 p.Asn706del Uncertain significance ★ same type
LRP4 p.Ile1119del Uncertain significance ★ 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/corin-p-ser669fs (accessed [today's date]).

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