Is CORIN p.Ala39Val (c.116C>T) pathogenic?

CORIN p.Ala39Val (c.116C>T) is classified Uncertain significance in CORIN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.0858); Ultra-rare (popmax 0.0187%, afr); Associated with Inborn genetic diseases.

What condition is associated with CORIN p.Ala39Val (c.116C>T)?

CORIN p.Ala39Val (c.116C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CORIN p.Ala39Val (c.116C>T) in the general population?

CORIN p.Ala39Val (c.116C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

What do computational predictors say about CORIN p.Ala39Val (c.116C>T)?

AlphaMissense predicts likely benign (score 0.0858) — an in-silico prediction, not a clinical call.

CORIN p.Ala39Val

c.116C>T · rs571200712 · VCV2397820

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0858 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0858	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -6.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.52, phastCons 0.98
Regional constraint	o/e 0.96	unconstrained · MANE · 242 kb · p 0.14 · regional, not allelic
Overall
CADD	8.823	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 0.0187% African / African-American · 14/75,036 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00903%

Overall 0.00775% 125/1,613,800 alleles · ultra-rare exomes 104/1,461,516 · genomes 21/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,360
Remaining individualsnot grpmax-eligible	0.0112%	8,925
European (non-Finnish)	0.00822%	12,163
South Asian	0.00549%	18,209
Admixed American	0.00167%	59,990
Finnishnot grpmax-eligible	0.00156%	64,008

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.Ala39Val
Coding: c.116C>T
MANE Select: NM_006587
dbSNP: rs571200712
Type: single nucleotide variant
Location: chr4:47806995 (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

LRP4 p.Leu39Pro Uncertain significance ★ ⚠ same residue
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

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-ala39val (accessed [today's date]).

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