Is MAPRE1 p.Ala129Ser (c.385G>T) pathogenic?

MAPRE1 p.Ala129Ser (c.385G>T) is classified Uncertain significance in MAPRE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely benign (0.1736); Very rare (popmax 0.000254%, nfe).

How common is MAPRE1 p.Ala129Ser (c.385G>T) in the general population?

MAPRE1 p.Ala129Ser (c.385G>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about MAPRE1 p.Ala129Ser (c.385G>T)?

AlphaMissense predicts likely benign (score 0.1736) — an in-silico prediction, not a clinical call.

MAPRE1 p.Ala129Ser

c.385G>T · VCV4103917

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1736 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1736	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -11.03	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 9,926 bp · p 0.39 · regional, not allelic
Overall
CADD	26.1	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 0.000254% European (non-Finnish) · 3/1,179,862 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,996 alleles · very rare exomes 3/1,461,682 · genomes 0/152,314 · 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: MAPRE1
Protein: p.Ala129Ser
Coding: c.385G>T
MANE Select: NM_012325
Type: single nucleotide variant
Location: chr20:32836751 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.65 · 33 PDB
Residue 129: an α-helix; the 'interaction with mtus2/tip150' region

Full MAPRE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPRE1 p.Ala138Gly Uncertain significance ★ ⚠ same type
MAPRE1 p.Arg162Lys Uncertain significance ★ ⚠ same type
MAPRE1 p.Arg222Gln Uncertain significance ★ ⚠ same type
MAPRE1 p.Arg222Trp Uncertain significance ★ ⚠ same type
MAPRE1 p.Asn104Ser Uncertain significance ★ ⚠ same type
MAPRE1 p.Asn188Ser Uncertain significance ★ ⚠ same type
MAPRE1 p.Asn201Ser Uncertain significance ★ ⚠ same type
MAPRE1 p.Asn25Ser 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/mapre1-p-ala129ser (accessed [today's date]).

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