Is CORIN p.Cys34Phe (c.101G>T) pathogenic?

CORIN p.Cys34Phe (c.101G>T) is classified Uncertain significance in CORIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). AlphaMissense: likely benign (0.1222); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CORIN p.Cys34Phe (c.101G>T)?

CORIN p.Cys34Phe (c.101G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CORIN p.Cys34Phe (c.101G>T) in the general population?

CORIN p.Cys34Phe (c.101G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CORIN p.Cys34Phe (c.101G>T)?

AlphaMissense predicts likely benign (score 0.1222) — an in-silico prediction, not a clinical call.

CORIN p.Cys34Phe

c.101G>T · VCV3835646

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1222 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1222	likely benign
REVEL	0.659	pathogenic-leaning
SaProt	LLR -6.11	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 242 kb · p 0.14 · regional, not allelic
Overall
CADD	24.5	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 0.00167% Admixed American · 1/59,966 alleles

Overall 6.84e-05% 1/1,461,616 alleles · very rare

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.Cys34Phe
Coding: c.101G>T
MANE Select: NM_006587
Type: single nucleotide variant
Location: chr4:47807010 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.20

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-cys34phe (accessed [today's date]).

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