Is MN1 p.Pro207Arg (c.620C>G) pathogenic?

MN1 p.Pro207Arg (c.620C>G) is classified Uncertain significance in MN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-08-06). AlphaMissense: ambiguous (0.4054); Very rare (popmax 8.5e-05%, nfe).

How common is MN1 p.Pro207Arg (c.620C>G) in the general population?

MN1 p.Pro207Arg (c.620C>G) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about MN1 p.Pro207Arg (c.620C>G)?

AlphaMissense predicts ambiguous (score 0.4054) — an in-silico prediction, not a clinical call.

MN1 p.Pro207Arg

c.620C>G · rs1198450862 · VCV1700416

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4054 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4054	ambiguous
REVEL	0.304	indeterminate
SaProt	LLR -6.96	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 50 kb · p 0.63 · regional, not allelic
Overall
CADD	24.9	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 8.5e-05% European (non-Finnish) · 1/1,175,900 alleles

Overall 6.24e-05% 1/1,603,026 alleles · very rare exomes 0/1,450,776 · genomes 1/152,250 · 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.Pro207Arg
Coding: c.620C>G
MANE Select: NM_002430
dbSNP: rs1198450862
Type: single nucleotide variant
Location: chr22:27799924 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 42.47
Residue 207: 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-pro207arg (accessed [today's date]).

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