Is ISCU p.Asp80= (c.240T>C) pathogenic?

ISCU p.Asp80= (c.240T>C) is classified Likely benign in ISCU (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). Absent from gnomAD v4.1.

How common is ISCU p.Asp80= (c.240T>C) in the general population?

ISCU p.Asp80= (c.240T>C) is absent from gnomAD v4.1 (gnomAD).

ISCU p.Asp80=

c.240T>C · VCV4704111

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -1.9	GERP -5.3
Overall
CADD	6.204	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: ISCU
Protein: p.Asp80=
Coding: c.240T>C
MANE Select: NM_213595
Type: single nucleotide variant
Location: chr12:108565332 (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-asp80 (accessed [today's date]).

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