Is RMND1 p.Val9Met (c.25G>A) pathogenic?

RMND1 p.Val9Met (c.25G>A) is classified Uncertain significance in RMND1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-03). AlphaMissense: likely benign (0.0813); Very rare (popmax 0.00801%, afr); Associated with combined oxidative phosphorylation defect type 11.

What condition is associated with RMND1 p.Val9Met (c.25G>A)?

RMND1 p.Val9Met (c.25G>A) is associated with combined oxidative phosphorylation defect type 11 (ClinVar).

How common is RMND1 p.Val9Met (c.25G>A) in the general population?

RMND1 p.Val9Met (c.25G>A) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about RMND1 p.Val9Met (c.25G>A)?

AlphaMissense predicts likely benign (score 0.0813) — an in-silico prediction, not a clinical call.

RMND1 p.Val9Met

Q: How is Combined oxidative phosphorylation defect type 11 inherited?

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

c.25G>A · VCV3593261

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0813 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

combined oxidative phosphorylation defect type 11

Computational evidence

Protein change
AlphaMissense	0.0813	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -8.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -0.77, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 41 kb · p 0.0012 · regional, not allelic
Overall
CADD	6.49	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

Grpmax group 0.00801% African / African-American · 6/74,892 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000807% 13/1,611,344 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,482
South Asian	0.0022%	45,524
Finnishnot grpmax-eligible	0.0016%	62,388
Remaining individualsnot grpmax-eligible	0.0016%	62,408
European (non-Finnish)	0.000254%	393,093

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: RMND1
Protein: p.Val9Met
Coding: c.25G>A
MANE Select: NM_017909
Type: single nucleotide variant
Location: chr6:151445787 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 70.28

Full RMND1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined oxidative phosphorylation defect type 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined oxidative phosphorylation defect type 11 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

RMND1 c.504+1G>A Pathogenic/Likely pathogenic ★★ same condition
RMND1 p.Arg23Ter Pathogenic/Likely pathogenic ★★ same condition
RMND1 p.Arg417Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
RMND1 p.Asn238Ser Pathogenic ★★ same condition
RMND1 p.Asp205Tyr Likely pathogenic ★★ ⚠ same condition
RMND1 p.Ter450Ser Pathogenic/Likely pathogenic ★★ same condition
RMND1 p.Tyr196Ter Likely pathogenic ★★ same condition
RMND1 c.1002+6T>C 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/rmnd1-p-val9met (accessed [today's date]).

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