Is MRPS23 p.Pro44Leu (c.131C>T) pathogenic?

MRPS23 p.Pro44Leu (c.131C>T) is classified Uncertain significance in MRPS23 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: likely pathogenic (0.5969); Very rare (popmax 0.00186%, nfe).

How common is MRPS23 p.Pro44Leu (c.131C>T) in the general population?

MRPS23 p.Pro44Leu (c.131C>T) is very rare (popmax 0.00186%, nfe) (gnomAD).

What do computational predictors say about MRPS23 p.Pro44Leu (c.131C>T)?

AlphaMissense predicts likely pathogenic (score 0.5969) — an in-silico prediction, not a clinical call.

MRPS23 p.Pro44Leu

c.131C>T · VCV4553312

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5969 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.5969	likely pathogenic
REVEL	0.575	indeterminate
SaProt	LLR -8.87	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 10 kb · p 0.73 · regional, not allelic
Overall
CADD	25.3	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 0.00186% European (non-Finnish) · 22/1,180,052 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00142% 23/1,614,094 alleles · very rare exomes 20/1,461,880 · genomes 3/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00186%	53,639
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: MRPS23
Protein: p.Pro44Leu
Coding: c.131C>T
MANE Select: NM_016070
Type: single nucleotide variant
Location: chr17:57849324 (GRCh38)
Gene constraint: LOEUF 1.117 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.21 · 85 PDB

Full MRPS23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MRPS23 p.Pro44= Benign ★ same residue
MRPS23 p.Arg42Lys Uncertain significance ★★ ⚠ same type
MRPS23 p.Arg98Trp Uncertain significance ★★ ⚠ same type
MRPS23 p.Ser14Phe Uncertain significance ★★ same type
MRPS23 c.215+12G>C Benign ★★ same type
MRPS23 p.Arg21= Likely benign ★★ same type
MRPS23 p.Gly136= Benign ★★ same type
MRPS23 p.His142= Benign/Likely benign ★★ 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/mrps23-p-pro44leu (accessed [today's date]).

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