Is MICU1 p.Arg129Pro (c.386G>C) pathogenic?

MICU1 p.Arg129Pro (c.386G>C) is classified Pathogenic/Likely pathogenic in MICU1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-07-27). AlphaMissense: likely pathogenic (0.9997); Ultra-rare (popmax 0.0176%, nfe); Associated with MICU1-related disorder.

What condition is associated with MICU1 p.Arg129Pro (c.386G>C)?

MICU1 p.Arg129Pro (c.386G>C) is associated with MICU1-related disorder, proximal myopathy with extrapyramidal signs (ClinVar).

How common is MICU1 p.Arg129Pro (c.386G>C) in the general population?

MICU1 p.Arg129Pro (c.386G>C) is ultra-rare (popmax 0.0176%, nfe) (gnomAD).

What do computational predictors say about MICU1 p.Arg129Pro (c.386G>C)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

MICU1 p.Arg129Pro

c.386G>C · rs375664373 · VCV279993

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MICU1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic ✓ concordant with ClinVar · top 2% in MICU1
REVEL	0.65	pathogenic-leaning
SaProt	LLR -17.26	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 199 kb · p 0.0006 · regional, not allelic
Overall
CADD	33.0	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 0.0176% European (non-Finnish) · 208/1,179,612 alleles

Filtering AF 0.0156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0149%

Overall 0.0145% 234/1,613,234 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0288%	3,469
European (non-Finnish)grpmax	0.0176%	5,671
Finnishnot grpmax-eligible	0.00781%	12,801
African / African-American	0.00401%	24,959

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MICU1
Protein: p.Arg129Pro
Coding: c.386G>C
MANE Select: NM_001195518
dbSNP: rs375664373
Type: single nucleotide variant
Location: chr10:72551286 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.82 · 12 PDB
Residue 129: a UniProt-annotated variant site (in mpxps); a UniProt-annotated variant site (in mpxps; uncertain significance); the 'k/r-ring' region; an α-helix

Full MICU1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MICU1-related disorder

Also linked: proximal myopathy with extrapyramidal signs

Similar variants

MICU1 p.Arg129Ter Pathogenic ★★ same residue
MICU1 c.1072-1G>C Pathogenic ★★ same condition
MICU1 c.161+1G>A Pathogenic/Likely pathogenic ★★ same condition
MICU1 c.735+1G>A Pathogenic/Likely pathogenic ★★ same condition
MICU1 c.933+2T>C Likely pathogenic ★★ same condition
MICU1 p.Arg119Ter Pathogenic ★★ same condition
MICU1 p.Arg154Ter Pathogenic/Likely pathogenic ★★ same condition
MICU1 p.Arg185Ter Pathogenic/Likely pathogenic ★★ 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/micu1-p-arg129pro (accessed [today's date]).

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