Is MN1 p.Val331Met (c.991G>A) pathogenic?

MN1 p.Val331Met (c.991G>A) is classified Uncertain significance in MN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-28). AlphaMissense: likely benign (0.1725); Very rare (popmax 0.00143%, afr); Associated with Inborn genetic diseases.

What condition is associated with MN1 p.Val331Met (c.991G>A)?

MN1 p.Val331Met (c.991G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MN1 p.Val331Met (c.991G>A) in the general population?

MN1 p.Val331Met (c.991G>A) is very rare (popmax 0.00143%, afr) (gnomAD).

What do computational predictors say about MN1 p.Val331Met (c.991G>A)?

AlphaMissense predicts likely benign (score 0.1725) — an in-silico prediction, not a clinical call.

MN1 p.Val331Met

c.991G>A · VCV3873880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1725 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00143%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1725	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -6.59	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 7.4	GERP 2.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 50 kb · p 0.63 · regional, not allelic
Overall
CADD	25.0	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 0.00143% African / African-American · 1/70,096 alleles

Filtering AF 0.000311% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000224%

Overall 0.000613% 9/1,468,636 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00143%	70,096
European (non-Finnish)	0.000722%	138,537

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.Val331Met
Coding: c.991G>A
MANE Select: NM_002430
Type: single nucleotide variant
Location: chr22:27799553 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 42.47
Residue 331: 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.Met323Thr Uncertain significance ★★ ⚠ same condition
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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-val331met (accessed [today's date]).

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