Is MN1 p.Ser373Pro (c.1117T>C) pathogenic?

MN1 p.Ser373Pro (c.1117T>C) is classified Uncertain significance in MN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-30). AlphaMissense: likely pathogenic (0.6675); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MN1 p.Ser373Pro (c.1117T>C)?

MN1 p.Ser373Pro (c.1117T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MN1 p.Ser373Pro (c.1117T>C) in the general population?

MN1 p.Ser373Pro (c.1117T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MN1 p.Ser373Pro (c.1117T>C)?

AlphaMissense predicts likely pathogenic (score 0.6675) — an in-silico prediction, not a clinical call.

MN1 p.Ser373Pro

c.1117T>C · rs2517773257 · VCV2231827

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6675 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6675	likely pathogenic
REVEL	0.239	benign-leaning
SaProt	LLR -7.50	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 50 kb · p 0.63 · regional, not allelic
Overall
CADD	22.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MN1
Protein: p.Ser373Pro
Coding: c.1117T>C
MANE Select: NM_002430
dbSNP: rs2517773257
Type: single nucleotide variant
Location: chr22:27799427 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 42.47
Residue 373: the 'disordered' region

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

MN1 p.Gly1092Arg Uncertain significance ★★ ⚠ same condition
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MN1 p.Gly613Arg Uncertain significance ★★ ⚠ same condition
MN1 p.Gly703Val Uncertain significance ★★ ⚠ same condition
MN1 p.Leu706Met Uncertain significance ★★ ⚠ same condition
MN1 p.Met323Thr Uncertain significance ★★ ⚠ same condition
MN1 p.Phe618Cys Uncertain significance ★★ ⚠ same condition
MN1 p.Pro1124Leu Uncertain significance ★★ ⚠ same condition

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-ser373pro (accessed [today's date]).

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