Is MTPAP p.Pro393Ser (c.1177C>T) pathogenic?

MTPAP p.Pro393Ser (c.1177C>T) is classified Uncertain significance in MTPAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely benign (0.3249); Absent from gnomAD v4.1.

How common is MTPAP p.Pro393Ser (c.1177C>T) in the general population?

MTPAP p.Pro393Ser (c.1177C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MTPAP p.Pro393Ser (c.1177C>T)?

AlphaMissense predicts likely benign (score 0.3249) — an in-silico prediction, not a clinical call.

MTPAP p.Pro393Ser

c.1177C>T · rs2538452398 · VCV2016300

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3249 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3249	likely benign
REVEL	0.416	indeterminate
SaProt	LLR -11.85	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 23 kb · p 5.5e-07 · regional, not allelic
Overall
CADD	24.4	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

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: MTPAP
Protein: p.Pro393Ser
Coding: c.1177C>T
MANE Select: NM_018109
dbSNP: rs2538452398
Type: single nucleotide variant
Location: chr10:30322433 (GRCh38)
Gene constraint: LOEUF 0.641 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 83.16 · 1 PDB

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

Similar variants

MTPAP p.Pro393Leu Uncertain significance ★ ⚠ same residue
MTPAP p.Pro393= Likely benign ★ same residue
MTPAP p.Asn478Asp Pathogenic ★★ ⚠ same type
MTPAP p.Ala141Thr Uncertain significance ★★ ⚠ same type
MTPAP p.Ala219Thr Uncertain significance ★★ ⚠ same type
MTPAP p.Arg160Trp Uncertain significance ★★ ⚠ same type
MTPAP p.Arg171Cys Uncertain significance ★★ ⚠ same type
MTPAP p.Arg461Gln 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/mtpap-p-pro393ser (accessed [today's date]).

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