Is ISCU p.Arg10Ser (c.30G>T) pathogenic?

ISCU p.Arg10Ser (c.30G>T) is classified Uncertain significance in ISCU (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-07). AlphaMissense: ambiguous (0.3781); Very rare (popmax 0.00147%, afr); Associated with Inborn genetic diseases.

What condition is associated with ISCU p.Arg10Ser (c.30G>T)?

ISCU p.Arg10Ser (c.30G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ISCU p.Arg10Ser (c.30G>T) in the general population?

ISCU p.Arg10Ser (c.30G>T) is very rare (popmax 0.00147%, afr) (gnomAD).

What do computational predictors say about ISCU p.Arg10Ser (c.30G>T)?

AlphaMissense predicts ambiguous (score 0.3781) — an in-silico prediction, not a clinical call.

ISCU p.Arg10Ser

c.30G>T · VCV3530175

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3781 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00147%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3781	ambiguous
REVEL	0.346	indeterminate
SaProt	LLR -5.48	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.68	GERP -3.4, phastCons 0.91
Regional constraint	o/e 1.10	unconstrained · MANE · 6,290 bp · p 0.16 · regional, not allelic
Overall
CADD	15.42	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

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

Overall 0.000205% 3/1,461,672 alleles · very rare exomes 3/1,309,372 · genomes 0/152,300 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00147%	68,248
South Asian	0.00136%	73,626
European (non-Finnish)	8.98e-05%	1,113,087

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.Arg10Ser
Coding: c.30G>T
MANE Select: NM_213595
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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ISCU p.Arg10Lys Uncertain significance ★ ⚠ same residue
ISCU p.Arg10= Likely benign ★ same residue
ISCU p.Ala13Val Uncertain significance ★★ ⚠ same condition
ISCU p.Ala15Thr Uncertain significance ★★ ⚠ same condition
ISCU p.Arg11Pro Uncertain significance ★★ ⚠ same condition
ISCU p.Arg11Trp Uncertain significance ★★ ⚠ same condition
ISCU p.Arg8Cys Uncertain significance ★★ ⚠ same condition
ISCU p.Lys166Asn 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/iscu-p-arg10ser (accessed [today's date]).

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