Is MN1 p.Ala481Val (c.1442C>T) pathogenic?

MN1 p.Ala481Val (c.1442C>T) is classified Likely benign in MN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-16). AlphaMissense: likely benign (0.1062); Very rare (popmax 0.00017%, nfe).

How common is MN1 p.Ala481Val (c.1442C>T) in the general population?

MN1 p.Ala481Val (c.1442C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about MN1 p.Ala481Val (c.1442C>T)?

AlphaMissense predicts likely benign (score 0.1062) — an in-silico prediction, not a clinical call.

MN1 p.Ala481Val

c.1442C>T · VCV3911518

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1062 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1062	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -6.92	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 6.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 50 kb · p 0.63 · regional, not allelic
Overall
CADD	22.9	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 0.00017% European (non-Finnish) · 2/1,173,960 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000125% 2/1,605,174 alleles · very rare exomes 2/1,452,838 · genomes 0/152,336 · joint denominator

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.Ala481Val
Coding: c.1442C>T
MANE Select: NM_002430
Type: single nucleotide variant
Location: chr22:27799102 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 42.47
Residue 481: a UniProt-annotated variant site (in cebalid); 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-ala481val (accessed [today's date]).

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