Is MN1 p.Pro353= (c.1059G>A) pathogenic?

MN1 p.Pro353= (c.1059G>A) is classified Likely benign in MN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-01). Low-frequency (popmax 1.29%, mid).

How common is MN1 p.Pro353= (c.1059G>A) in the general population?

MN1 p.Pro353= (c.1059G>A) is low-frequency (popmax 1.29%, mid) (gnomAD).

MN1 p.Pro353=

c.1059G>A · rs45463494 · VCV2571154

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.29%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.8	GERP -1.4, phastCons 0.009
Overall
CADD	6.942	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.29% Middle Eastern · 62/4,820 alleles

Filtering AF 1.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.937%

Overall 0.424% 6,162/1,452,772 alleles · low-frequency exomes 5,499/1,301,010 · genomes 663/151,762 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.07%	48
Middle Easterngrpmax	1.29%	78
Ashkenazi Jewishnot grpmax-eligible	1.06%	95
European (non-Finnish)	0.389%	257
Remaining individualsnot grpmax-eligible	0.383%	261
Admixed American	0.201%	496
South Asian	0.182%	548
African / African-American	0.082%	1,219
East Asian	0.00252%	39,660

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: MN1
Protein: p.Pro353=
Coding: c.1059G>A
MANE Select: NM_002430
dbSNP: rs45463494
Type: single nucleotide variant
Location: chr22:27799485 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 42.47
Residue 353: the 'disordered' region

Full MN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MN1 p.Gln1273Ter Pathogenic ★★ same type
MN1 p.Lys455Ter Likely pathogenic ★★ same type
MN1 p.Trp1248Ter Pathogenic/Likely pathogenic ★★ same type
MN1 p.Ala38Asp Uncertain significance ★★ ⚠ same type
MN1 p.Gly1092Arg Uncertain significance ★★ ⚠ same type
MN1 p.Gly120Val Uncertain significance ★★ ⚠ same type
MN1 p.Gly161Arg Uncertain significance ★★ ⚠ same type
MN1 p.Gly613Arg 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/mn1-p-pro353 (accessed [today's date]).

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