Is ISCU p.Arg10= (c.30G>A) pathogenic?

ISCU p.Arg10= (c.30G>A) is classified Likely benign in ISCU (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-04). Very rare (popmax 0.00147%, afr).

How common is ISCU p.Arg10= (c.30G>A) in the general population?

ISCU p.Arg10= (c.30G>A) is very rare (popmax 0.00147%, afr) (gnomAD).

ISCU p.Arg10=

c.30G>A · rs776009693 · VCV1664632

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00147%, afr)

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 0.68	GERP -3.4, phastCons 0.91
Overall
CADD	6.659	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00147% African / African-American · 1/68,248 alleles

Filtering AF 7.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000274% 4/1,461,672 alleles · very rare exomes 4/1,309,372 · genomes 0/152,300 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00147%	68,248
European (non-Finnish)	0.00027%	371,030

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.Arg10=
Coding: c.30G>A
MANE Select: NM_213595
dbSNP: rs776009693
Type: single nucleotide variant
Location: chr12:108562652 (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 p.Arg10Lys Uncertain significance ★ ⚠ same residue
ISCU p.Arg10Ser Uncertain significance ★ same residue
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

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-arg10 (accessed [today's date]).

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