Is CORIN p.Phe874Ser (c.2621T>C) pathogenic?

CORIN p.Phe874Ser (c.2621T>C) is classified Uncertain significance in CORIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: likely benign (0.0697); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CORIN p.Phe874Ser (c.2621T>C)?

CORIN p.Phe874Ser (c.2621T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CORIN p.Phe874Ser (c.2621T>C) in the general population?

CORIN p.Phe874Ser (c.2621T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CORIN p.Phe874Ser (c.2621T>C)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

CORIN p.Phe874Ser

c.2621T>C · VCV4005871

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -3.44	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -4, phastCons 0.65
Regional constraint	o/e 0.96	unconstrained · MANE · 242 kb · p 0.14 · regional, not allelic
Overall
CADD	11.55	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,016 alleles

Overall 6.2e-05% 1/1,614,168 alleles · very rare exomes 1/1,461,878 · genomes 0/152,290 · joint denominator

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.Phe874Ser
Coding: c.2621T>C
MANE Select: NM_006587
Type: single nucleotide variant
Location: chr4:47603588 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.20
Residue 874: 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-phe874ser (accessed [today's date]).

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