Is MN1 p.Arg995Ser (c.2983C>A) pathogenic?

MN1 p.Arg995Ser (c.2983C>A) is classified Uncertain significance in MN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-18). AlphaMissense: ambiguous (0.4555); No allele count reported in gnomAD v4.1 (AN 1,607,124).

How common is MN1 p.Arg995Ser (c.2983C>A) in the general population?

MN1 p.Arg995Ser (c.2983C>A) is no allele count reported in gnomAD v4.1 (AN 1,607,124) (gnomAD).

What do computational predictors say about MN1 p.Arg995Ser (c.2983C>A)?

AlphaMissense predicts ambiguous (score 0.4555) — an in-silico prediction, not a clinical call.

MN1 p.Arg995Ser

c.2983C>A · rs1383826053 · VCV2573952

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4555 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,607,124)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4555	ambiguous
REVEL	0.223	benign-leaning
SaProt	LLR -4.96	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 50 kb · p 0.63 · regional, not allelic
Overall
CADD	25.8	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

No allele count reported in gnomAD v4.1 (AN 1,607,124). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MN1
Protein: p.Arg995Ser
Coding: c.2983C>A
MANE Select: NM_002430
dbSNP: rs1383826053
Type: single nucleotide variant
Location: chr22:27797561 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 42.47
Residue 995: 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.Arg995His Uncertain significance ★ ⚠ same residue
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

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-arg995ser (accessed [today's date]).

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