Is CORIN p.Gln246= (c.738A>G) pathogenic?

CORIN p.Gln246= (c.738A>G) is classified Likely benign in CORIN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-22). Rare (popmax 0.661%, sas); Associated with CORIN-related disorder.

What condition is associated with CORIN p.Gln246= (c.738A>G)?

CORIN p.Gln246= (c.738A>G) is associated with CORIN-related disorder (ClinVar).

How common is CORIN p.Gln246= (c.738A>G) in the general population?

CORIN p.Gln246= (c.738A>G) is rare (popmax 0.661%, sas) (gnomAD).

CORIN p.Gln246=

c.738A>G · rs567348021 · VCV3043193

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.661%, sas)

Conditions

CORIN-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.048	GERP -2, phastCons 0.044
Overall
CADD	4.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.661% South Asian · 602/91,070 alleles

Filtering AF 0.617% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.6%

Overall 0.039% 630/1,614,138 alleles · rare exomes 595/1,461,856 · genomes 35/152,282 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.661%	151
Remaining individualsnot grpmax-eligible	0.0432%	2,315
Admixed American	0.00167%	60,022

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.Gln246=
Coding: c.738A>G
MANE Select: NM_006587
dbSNP: rs567348021
Type: single nucleotide variant
Location: chr4:47744463 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.20
Residue 246: the fz 1 domain

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

Disease context

CORIN-related disorder

Similar variants

LRP4 p.Ala246= Likely benign ★ same residue
LRP4 c.316+1G>A Pathogenic ★★ same condition
LRP4 p.Arg1327Gln Uncertain significance ★★ ⚠ same condition
LRP4 p.Gly1515Ala Uncertain significance ★★ ⚠ same condition
LRP4 p.Pro1307Ser Uncertain significance ★★ ⚠ same condition
LRP4 c.2613-2A>T Pathogenic ★ same condition
LRP4 p.Arg632His Likely pathogenic ★ same condition
LRP4 p.Trp1487Ter Likely pathogenic ★ 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-gln246 (accessed [today's date]).

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