Is MRPS7 p.Ala2Val (c.5C>T) pathogenic?

MRPS7 p.Ala2Val (c.5C>T) is classified Benign in MRPS7 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). AlphaMissense: ambiguous (0.3665); Common (popmax 88%, eas) — too common for a highly-penetrant pathogenic allele; Associated with combined oxidative phosphorylation deficiency 34.

What condition is associated with MRPS7 p.Ala2Val (c.5C>T)?

MRPS7 p.Ala2Val (c.5C>T) is associated with combined oxidative phosphorylation deficiency 34 (ClinVar).

What do computational predictors say about MRPS7 p.Ala2Val (c.5C>T)?

AlphaMissense predicts ambiguous (score 0.3665) — an in-silico prediction, not a clinical call.

MRPS7 p.Ala2Val

Q: How common is MRPS7 p.Ala2Val (c.5C>T) in the general population?

MRPS7 p.Ala2Val (c.5C>T) is common (popmax 88%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Syndromic sensorineural deafness due to combined oxidative phosphorylation defect inherited?

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

c.5C>T · rs8075276 · VCV379995

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.3665 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 88%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

combined oxidative phosphorylation deficiency 34

Computational evidence

Protein change
AlphaMissense	0.3665	ambiguous
REVEL	0.083	moderately benign-leaning
SaProt	LLR -9.25	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.8	GERP 0.49, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 4,019 bp · p 0.74 · regional, not allelic
Overall
CADD	27.0	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 88% East Asian · 39,441/44,812 alleles

Filtering AF 87.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 87%

Overall 80.4% 1,292,169/1,608,006 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	89.8%	1
East Asiangrpmax	88%	1
Amishnot grpmax-eligible	84.2%	1
South Asian	83.6%	1
European (non-Finnish)	82.7%	1
Admixed American	81.2%	1
Remaining individualsnot grpmax-eligible	78.5%	1
Ashkenazi Jewishnot grpmax-eligible	73%	1
Middle Eastern	68.7%	1
African / African-American	32.4%	3

Finnish 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: MRPS7
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_138619 · reported on NM_015971
dbSNP: rs8075276
Type: single nucleotide variant
Location: chr17:75261905 (GRCh38)

Full MRPS7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined oxidative phosphorylation deficiency 34 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Syndromic sensorineural deafness due to combined oxidative phosphorylation defect (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

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/mrps7-p-ala2val (accessed [today's date]).

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