Is CORIN p.Val896Ala (c.2687T>C) pathogenic?

CORIN p.Val896Ala (c.2687T>C) is classified Uncertain significance in CORIN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). AlphaMissense: ambiguous (0.5023); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with CORIN p.Val896Ala (c.2687T>C)?

CORIN p.Val896Ala (c.2687T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CORIN p.Val896Ala (c.2687T>C) in the general population?

CORIN p.Val896Ala (c.2687T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CORIN p.Val896Ala (c.2687T>C)?

AlphaMissense predicts ambiguous (score 0.5023) — an in-silico prediction, not a clinical call.

CORIN p.Val896Ala

c.2687T>C · VCV3496064

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5023 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5023	ambiguous
REVEL	0.4	indeterminate
SaProt	LLR -10.65	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 242 kb · p 0.14 · regional, not allelic
Overall
CADD	21.8	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

Grpmax group 0.00223% East Asian · 1/44,872 alleles

Overall 0.000186% 3/1,614,142 alleles · very rare exomes 3/1,461,872 · genomes 0/152,270 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,872
Finnishnot grpmax-eligible	0.00156%	64,034
African / African-American	0.00133%	75,040

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.Val896Ala
Coding: c.2687T>C
MANE Select: NM_006587
Type: single nucleotide variant
Location: chr4:47603522 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.20
Residue 896: 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-val896ala (accessed [today's date]).

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