Is MRPL12 p.Pro3Ser (c.7C>T) pathogenic?

MRPL12 p.Pro3Ser (c.7C>T) is classified Likely benign in MRPL12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely benign (0.0885); Rare (popmax 0.354%, afr).

How common is MRPL12 p.Pro3Ser (c.7C>T) in the general population?

MRPL12 p.Pro3Ser (c.7C>T) is rare (popmax 0.354%, afr) (gnomAD).

What do computational predictors say about MRPL12 p.Pro3Ser (c.7C>T)?

AlphaMissense predicts likely benign (score 0.0885) — an in-silico prediction, not a clinical call.

MRPL12 p.Pro3Ser

c.7C>T · rs8074290 · VCV2042837

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0885 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.354%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0885	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -5.94	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 1.3	GERP -0.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 3,735 bp · p 0.28 · regional, not allelic
Overall
CADD	21.0	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 0.354% African / African-American · 242/68,450 alleles

Filtering AF 0.317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.303%

Overall 0.0203% 302/1,485,278 alleles · rare exomes 141/1,332,912 · genomes 161/152,366 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.354%	283
Middle Eastern	0.06%	1,667
Remaining individualsnot grpmax-eligible	0.0453%	2,207
Admixed American	0.0313%	3,190
South Asian	0.00377%	26,508
European (non-Finnish)	0.00125%	80,274

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: MRPL12
Protein: p.Pro3Ser
Coding: c.7C>T
MANE Select: NM_002949
dbSNP: rs8074290
Type: single nucleotide variant
Location: chr17:81703508 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.55 · 46 PDB

Full MRPL12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MRPL12 p.Ala124Pro Uncertain significance ★★ ⚠ same type
MRPL12 p.Ala124Val Uncertain significance ★★ ⚠ same type
MRPL12 p.Ala33Thr Uncertain significance ★★ ⚠ same type
MRPL12 p.Arg127Trp Uncertain significance ★★ ⚠ same type
MRPL12 p.Arg133His Uncertain significance ★★ ⚠ same type
MRPL12 p.Ile149Val Uncertain significance ★★ ⚠ same type
MRPL12 p.Leu76Pro Uncertain significance ★★ ⚠ same type
MRPL12 p.Pro12Arg 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/mrpl12-p-pro3ser (accessed [today's date]).

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