Is MTPAP p.Phe355Ser (c.1064T>C) pathogenic?

MTPAP p.Phe355Ser (c.1064T>C) is classified Uncertain significance in MTPAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely pathogenic (0.7821); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MTPAP p.Phe355Ser (c.1064T>C)?

MTPAP p.Phe355Ser (c.1064T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MTPAP p.Phe355Ser (c.1064T>C) in the general population?

MTPAP p.Phe355Ser (c.1064T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MTPAP p.Phe355Ser (c.1064T>C)?

AlphaMissense predicts likely pathogenic (score 0.7821) — an in-silico prediction, not a clinical call.

MTPAP p.Phe355Ser

c.1064T>C · VCV4625312

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7821 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7821	likely pathogenic
REVEL	0.388	indeterminate
SaProt	LLR -8.97	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 0.8, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 23 kb · p 5.5e-07 · regional, not allelic
Overall
CADD	21.9	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

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.Phe355Ser
Coding: c.1064T>C
MANE Select: NM_018109
Type: single nucleotide variant
Location: chr10:30322546 (GRCh38)
Gene constraint: LOEUF 0.641 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 83.16 · 1 PDB
Residue 355: an α-helix

Full MTPAP 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

MTPAP p.Ala141Thr Uncertain significance ★★ ⚠ same condition
MTPAP p.Arg160Trp Uncertain significance ★★ ⚠ same condition
MTPAP p.Arg171Cys Uncertain significance ★★ ⚠ same condition
MTPAP p.Arg461Gln Uncertain significance ★★ ⚠ same condition
MTPAP p.Asn167Ser Uncertain significance ★★ ⚠ same condition
MTPAP p.Asn522Ser Uncertain significance ★★ ⚠ same condition
MTPAP p.Asn556Thr Uncertain significance ★★ ⚠ same condition
MTPAP p.Cys119Tyr 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/mtpap-p-phe355ser (accessed [today's date]).

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