What condition is associated with ISCA1 p.Arg7Pro (c.20G>C)?

ISCA1 p.Arg7Pro (c.20G>C) is associated with multiple mitochondrial dysfunctions syndrome 5 (ClinVar).

How common is ISCA1 p.Arg7Pro (c.20G>C) in the general population?

ISCA1 p.Arg7Pro (c.20G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ISCA1 p.Arg7Pro (c.20G>C)?

AlphaMissense predicts likely pathogenic (score 0.6069) — an in-silico prediction, not a clinical call.

ISCA1 p.Arg7Pro

Q: Is ISCA1 p.Arg7Pro (c.20G>C) pathogenic?

ISCA1 p.Arg7Pro (c.20G>C) is classified Uncertain significance in ISCA1 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.6069); Absent from gnomAD v4.1; Associated with multiple mitochondrial dysfunctions syndrome 5.

Q: How is Multiple mitochondrial dysfunctions syndrome type 5 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.20G>C · rs766827180 · VCV2585244

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6069 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

multiple mitochondrial dysfunctions syndrome 5

Computational evidence

Protein change
AlphaMissense	0.6069	likely pathogenic
REVEL	0.333	indeterminate
SaProt	LLR -9.98	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 16 kb · p 8.6e-05 · regional, not allelic
Overall
CADD	27.1	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

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: ISCA1
Protein: p.Arg7Pro
Coding: c.20G>C
MANE Select: NM_030940
dbSNP: rs766827180
Type: single nucleotide variant
Location: chr9:86282439 (GRCh38)
Gene constraint: LOEUF 1.785 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.18

Full ISCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

multiple mitochondrial dysfunctions syndrome 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multiple mitochondrial dysfunctions syndrome type 5 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

ISCA1 p.Glu87Lys Conflicting classifications of pathogenicity ★ ⚠ same condition
ISCA1 p.Val10Gly Pathogenic ⚠ same condition
ISCA1 c.241+92G>A Benign ★★ same type
ISCA1 p.Asn116= Benign ★★ same type
ISCA1 p.Val111= Likely benign ★★ same type
ISCA1 p.Ala31Thr Uncertain significance ★ ⚠ same type
ISCA1 p.Ala8Ser Uncertain significance ★ ⚠ same type
ISCA1 p.Arg83Lys 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/isca1-p-arg7pro (accessed [today's date]).

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