Is MN1 p.Phe203Ser (c.608T>C) pathogenic?

MN1 p.Phe203Ser (c.608T>C) is classified Uncertain significance in MN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-06). AlphaMissense: likely pathogenic (0.9878); Very rare (popmax 0.00335%, amr); Associated with Inborn genetic diseases.

What condition is associated with MN1 p.Phe203Ser (c.608T>C)?

MN1 p.Phe203Ser (c.608T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MN1 p.Phe203Ser (c.608T>C) in the general population?

MN1 p.Phe203Ser (c.608T>C) is very rare (popmax 0.00335%, amr) (gnomAD).

What do computational predictors say about MN1 p.Phe203Ser (c.608T>C)?

AlphaMissense predicts likely pathogenic (score 0.9878) — an in-silico prediction, not a clinical call.

MN1 p.Phe203Ser

c.608T>C · rs749706989 · VCV2533912

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9878 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00335%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9878	likely pathogenic · top 4% in MN1
REVEL	0.486	indeterminate
SaProt	LLR -6.10	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL 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 2.2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 50 kb · p 0.63 · regional, not allelic
Overall
CADD	27.9	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 0.00335% Admixed American · 2/59,636 alleles

Filtering AF 0.000556% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000208%

Overall 0.000125% 2/1,603,512 alleles · very rare exomes 2/1,451,184 · genomes 0/152,328 · 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.Phe203Ser
Coding: c.608T>C
MANE Select: NM_002430
dbSNP: rs749706989
Type: single nucleotide variant
Location: chr22:27799936 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 42.47
Residue 203: 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
MN1 p.Phe618Cys Uncertain significance ★★ ⚠ same condition
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-phe203ser (accessed [today's date]).

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