Is NDUFS8 p.Arg2Pro (c.5G>C) pathogenic?

NDUFS8 p.Arg2Pro (c.5G>C) is classified Uncertain significance in NDUFS8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely benign (0.1036); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with NDUFS8 p.Arg2Pro (c.5G>C)?

NDUFS8 p.Arg2Pro (c.5G>C) is associated with Inborn genetic diseases (ClinVar).

How common is NDUFS8 p.Arg2Pro (c.5G>C) in the general population?

NDUFS8 p.Arg2Pro (c.5G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NDUFS8 p.Arg2Pro (c.5G>C)?

AlphaMissense predicts likely benign (score 0.1036) — an in-silico prediction, not a clinical call.

NDUFS8 p.Arg2Pro

c.5G>C · VCV4118330

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1036 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1036	likely benign
REVEL	0.45	indeterminate
SaProt	LLR -7.79	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.031	phastCons 0.004
Regional constraint	o/e 0.85	unconstrained · MANE · 4,438 bp · p 0.011 · regional, not allelic
Overall
CADD	15.49	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: NDUFS8
Protein: p.Arg2Pro
Coding: c.5G>C
MANE Select: NM_002496
Type: single nucleotide variant
Location: chr11:68032156 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI 0.03 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.73 · 7 PDB

Full NDUFS8 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

NDUFS8 p.Arg2Leu Uncertain significance ★ ⚠ same residue
NDUFS8 p.Arg2Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
NDUFS8 p.Arg2His Uncertain significance ★ ⚠ same residue
NDUFS8 p.Arg54Gln Uncertain significance ★★ ⚠ same condition
NDUFS8 p.Asn184Ile Uncertain significance ★★ ⚠ same condition
NDUFS8 p.Glu198Lys Uncertain significance ★★ ⚠ same condition
NDUFS8 p.Pro22Ser Uncertain significance ★★ ⚠ same condition
NDUFS8 p.Ala123Thr 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/ndufs8-p-arg2pro (accessed [today's date]).

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