Is MRNIP p.Asp331= (c.993C>T) pathogenic?

MRNIP p.Asp331= (c.993C>T) is classified Conflicting classifications of pathogenicity in MRNIP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-04-01). Ultra-rare (popmax 0.0955%, nfe); Associated with Paget disease of bone 3.

What condition is associated with MRNIP p.Asp331= (c.993C>T)?

MRNIP p.Asp331= (c.993C>T) is associated with Paget disease of bone 3 (ClinVar).

How common is MRNIP p.Asp331= (c.993C>T) in the general population?

MRNIP p.Asp331= (c.993C>T) is ultra-rare (popmax 0.0955%, nfe) (gnomAD).

MRNIP p.Asp331=

c.993C>T · rs148611524 · VCV353178

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0955%, nfe)

Conditions

Paget disease of bone 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.95	GERP -0.59, phastCons 0.48
Overall
CADD	1.591	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0955% European (non-Finnish) · 1,123/1,175,884 alleles

Filtering AF 0.0909% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.089%

Overall 0.0757% 1,217/1,606,654 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0955%	1,047
Admixed American	0.0593%	1,687
Remaining individualsnot grpmax-eligible	0.0483%	2,069
African / African-American	0.0268%	3,734
Ashkenazi Jewishnot grpmax-eligible	0.0173%	5,794
Finnishnot grpmax-eligible	0.0047%	21,269
South Asian	0.00111%	90,450

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: MRNIP
Protein: p.Asp331=
Coding: c.993C>T
MANE Select: NM_003900 · reported on NM_016175
dbSNP: rs148611524
Type: single nucleotide variant
Location: chr5:179837430 (GRCh38)

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

Disease context

Paget disease of bone 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/mrnip-p-asp331 (accessed [today's date]).

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