Is SPINK5 p.Ala487= (c.1461T>C) pathogenic?

SPINK5 p.Ala487= (c.1461T>C) is classified Likely benign in SPINK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). Absent from gnomAD v4.1; Associated with ichthyosis linearis circumflexa.

What condition is associated with SPINK5 p.Ala487= (c.1461T>C)?

SPINK5 p.Ala487= (c.1461T>C) is associated with ichthyosis linearis circumflexa (ClinVar).

How common is SPINK5 p.Ala487= (c.1461T>C) in the general population?

SPINK5 p.Ala487= (c.1461T>C) is absent from gnomAD v4.1 (gnomAD).

SPINK5 p.Ala487=

c.1461T>C · rs750918436 · VCV756520

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ichthyosis linearis circumflexa

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 0.22	GERP -0.97, phastCons 0.07
Overall
CADD	8.413	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SPINK5
Protein: p.Ala487=
Coding: c.1461T>C
MANE Select: NM_006846
dbSNP: rs750918436
Type: single nucleotide variant
Location: chr5:148104982 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.37 · 6 PDB
Residue 487: the kazal-like 7 domain

Full SPINK5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ichthyosis linearis circumflexa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SPINK5 c.1302+4A>T Pathogenic ★★ same condition
SPINK5 c.1430+1G>T Pathogenic/Likely pathogenic ★★ same condition
SPINK5 c.1431-12G>A Pathogenic/Likely pathogenic ★★ same condition
SPINK5 c.2240+1G>A Pathogenic ★★ same condition
SPINK5 c.2740-1G>C Likely pathogenic ★★ same condition
SPINK5 c.666+1G>A Pathogenic/Likely pathogenic ★★ same condition
SPINK5 c.81+2T>A Pathogenic ★★ same condition
SPINK5 c.81+5G>A Pathogenic/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/spink5-p-ala487 (accessed [today's date]).

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