Is MN1 p.Ala997Pro (c.2989G>C) pathogenic?

MN1 p.Ala997Pro (c.2989G>C) is classified Uncertain significance in MN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). AlphaMissense: likely benign (0.1214); Ultra-rare (popmax 0.0151%, amr); Associated with Inborn genetic diseases.

What condition is associated with MN1 p.Ala997Pro (c.2989G>C)?

MN1 p.Ala997Pro (c.2989G>C) is associated with Inborn genetic diseases (ClinVar).

How common is MN1 p.Ala997Pro (c.2989G>C) in the general population?

MN1 p.Ala997Pro (c.2989G>C) is ultra-rare (popmax 0.0151%, amr) (gnomAD).

What do computational predictors say about MN1 p.Ala997Pro (c.2989G>C)?

AlphaMissense predicts likely benign (score 0.1214) — an in-silico prediction, not a clinical call.

MN1 p.Ala997Pro

c.2989G>C · VCV3873869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1214 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0151%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1214	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -5.82	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 4.9	GERP 0.65, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 50 kb · p 0.63 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0151% Admixed American · 9/59,614 alleles

Filtering AF 0.00778% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00582%

Overall 0.000622% 10/1,607,130 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0151%	6,624
European (non-Finnish)	8.49e-05%	1,177,849

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.Ala997Pro
Coding: c.2989G>C
MANE Select: NM_002430
Type: single nucleotide variant
Location: chr22:27797555 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 42.47
Residue 997: a UniProt-annotated variant site (in cebalid); 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

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MN1 p.Leu706Met Uncertain significance ★★ ⚠ same condition
MN1 p.Met323Thr Uncertain significance ★★ ⚠ same condition
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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-ala997pro (accessed [today's date]).

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