Is ISCU p.Lys82= (c.246G>A) pathogenic?

ISCU p.Lys82= (c.246G>A) is classified Likely benign in ISCU (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). Very rare (popmax 8.48e-05%, nfe).

How common is ISCU p.Lys82= (c.246G>A) in the general population?

ISCU p.Lys82= (c.246G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

ISCU p.Lys82=

c.246G>A · rs2030840082 · VCV1554074

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 2.8	GERP -1.2, phastCons 1
Overall
CADD	9.173	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,822 alleles

Overall 6.2e-05% 1/1,613,964 alleles · very rare exomes 1/1,461,628 · genomes 0/152,336 · 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: ISCU
Protein: p.Lys82=
Coding: c.246G>A
MANE Select: NM_213595
dbSNP: rs2030840082
Type: single nucleotide variant
Location: chr12:108565338 (GRCh38)
Gene constraint: LOEUF 1.542 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.17 · 18 PDB

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

Similar variants

ISCU c.418+382G>C Pathogenic ★★ same type
ISCU p.Ala105Gly Uncertain significance ★★ ⚠ same type
ISCU p.Ala13Val Uncertain significance ★★ ⚠ same type
ISCU p.Ala149Thr Uncertain significance ★★ ⚠ same type
ISCU p.Ala15Thr Uncertain significance ★★ ⚠ same type
ISCU p.Ala30Val Uncertain significance ★★ ⚠ same type
ISCU p.Ala6Val Uncertain significance ★★ ⚠ same type
ISCU p.Arg11Pro Uncertain significance ★★ ⚠ same type

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/iscu-p-lys82 (accessed [today's date]).

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