Is MN1 p.Pro449Arg (c.1346C>G) pathogenic?

MN1 p.Pro449Arg (c.1346C>G) is classified Likely benign in MN1 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-09-12). AlphaMissense: likely pathogenic (0.759); Rare (popmax 0.123%, afr); Associated with Inborn genetic diseases.

What condition is associated with MN1 p.Pro449Arg (c.1346C>G)?

MN1 p.Pro449Arg (c.1346C>G) is associated with Inborn genetic diseases (ClinVar).

How common is MN1 p.Pro449Arg (c.1346C>G) in the general population?

MN1 p.Pro449Arg (c.1346C>G) is rare (popmax 0.123%, afr) (gnomAD).

What do computational predictors say about MN1 p.Pro449Arg (c.1346C>G)?

AlphaMissense predicts likely pathogenic (score 0.759) — an in-silico prediction, not a clinical call.

MN1 p.Pro449Arg

c.1346C>G · rs543407693 · VCV2374713

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.759 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.123%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.759	likely pathogenic
REVEL	0.483	indeterminate
SaProt	LLR -8.42	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 50 kb · p 0.63 · regional, not allelic
Overall
CADD	27.3	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 0.123% African / African-American · 92/74,912 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0949%

Overall 0.0141% 227/1,605,096 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.123%	814
East Asian	0.0404%	2,478
Admixed American	0.0302%	3,311
Remaining individualsnot grpmax-eligible	0.0129%	7,755
European (non-Finnish)	0.00733%	13,651
South Asian	0.00552%	18,130

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.Pro449Arg
Coding: c.1346C>G
MANE Select: NM_002430
dbSNP: rs543407693
Type: single nucleotide variant
Location: chr22:27799198 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 42.47

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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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-pro449arg (accessed [today's date]).

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