Is MAPRE2 p.Ser50Phe (c.149C>T) pathogenic?

MAPRE2 p.Ser50Phe (c.149C>T) is classified Uncertain significance in MAPRE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-03). AlphaMissense: likely pathogenic (0.9478); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MAPRE2 p.Ser50Phe (c.149C>T)?

MAPRE2 p.Ser50Phe (c.149C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MAPRE2 p.Ser50Phe (c.149C>T) in the general population?

MAPRE2 p.Ser50Phe (c.149C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPRE2 p.Ser50Phe (c.149C>T)?

AlphaMissense predicts likely pathogenic (score 0.9478) — an in-silico prediction, not a clinical call.

MAPRE2 p.Ser50Phe

c.149C>T · VCV4840897

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9478 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9478	likely pathogenic
REVEL	0.529	indeterminate
SaProt	LLR -12.61	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.9, phastCons 1
Regional constraint	o/e 0.26	constrained · MANE · 61 kb · p 5.4e-31 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAPRE2
Protein: p.Ser50Phe
Coding: c.149C>T
MANE Select: NM_014268
Type: single nucleotide variant
Location: chr18:35070221 (GRCh38)
Gene constraint: LOEUF 0.494 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 75.12

Full MAPRE2 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

MAPRE2 p.Glu318Lys Uncertain significance ★★ ⚠ same condition
MAPRE2 p.Ser28Ter Uncertain significance ★★ same condition
MAPRE2 c.123-6T>C Uncertain significance ★ same condition
MAPRE2 p.Arg143His Uncertain significance ★ ⚠ same condition
MAPRE2 p.Arg220Gln Uncertain significance ★ ⚠ same condition
MAPRE2 p.Gln174Glu Uncertain significance ★ ⚠ same condition
MAPRE2 p.Gln291Arg Uncertain significance ★ ⚠ same condition
MAPRE2 p.Glu309Val 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/mapre2-p-ser50phe (accessed [today's date]).

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