Is MRPS7 p.Pro175Ser (c.523C>T) pathogenic?

MRPS7 p.Pro175Ser (c.523C>T) is classified Uncertain significance in MRPS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.0706); Very rare (popmax 0.00934%, afr).

How common is MRPS7 p.Pro175Ser (c.523C>T) in the general population?

MRPS7 p.Pro175Ser (c.523C>T) is very rare (popmax 0.00934%, afr) (gnomAD).

What do computational predictors say about MRPS7 p.Pro175Ser (c.523C>T)?

AlphaMissense predicts likely benign (score 0.0706) — an in-silico prediction, not a clinical call.

MRPS7 p.Pro175Ser

c.523C>T · VCV4542217

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0706 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0706	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -4.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.49	GERP -3.7
Regional constraint	o/e 1.02	unconstrained · MANE · 4,019 bp · p 0.74 · regional, not allelic
Overall
CADD	0.271	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 0.00934% African / African-American · 7/74,946 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000434% 7/1,613,880 alleles · very rare exomes 1/1,461,632 · genomes 6/152,248 · joint denominator

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.Pro175Ser
Coding: c.523C>T
MANE Select: NM_015971
Type: single nucleotide variant
Location: chr17:75265717 (GRCh38)
Gene constraint: LOEUF 0.758 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 87.29 · 86 PDB

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

Similar variants

MRPS7 p.Pro175Ala Likely benign ★ same residue
MRPS7 p.Arg166Cys Uncertain significance ★★ ⚠ same type
MRPS7 p.Arg192Gln Uncertain significance ★★ ⚠ same type
MRPS7 p.Arg192Trp Uncertain significance ★★ ⚠ same type
MRPS7 p.Arg21Gln Uncertain significance ★★ ⚠ same type
MRPS7 p.Arg240Cys Uncertain significance ★★ ⚠ same type
MRPS7 p.Glu138Lys Uncertain significance ★★ ⚠ same type
MRPS7 p.Glu67Gln 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/mrps7-p-pro175ser (accessed [today's date]).

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