Is MTPAP p.Pro83Ser (c.247C>T) pathogenic?

MTPAP p.Pro83Ser (c.247C>T) is classified Uncertain significance in MTPAP (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-28). AlphaMissense: likely benign (0.159); Very rare (popmax 0.000763%, nfe).

How common is MTPAP p.Pro83Ser (c.247C>T) in the general population?

MTPAP p.Pro83Ser (c.247C>T) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about MTPAP p.Pro83Ser (c.247C>T)?

AlphaMissense predicts likely benign (score 0.159) — an in-silico prediction, not a clinical call.

MTPAP p.Pro83Ser

c.247C>T · rs372003224 · VCV586158

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.159 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.159	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -9.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 7,745 bp · p 0.2 · regional, not allelic
Overall
CADD	18.91	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.000763% European (non-Finnish) · 9/1,179,954 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,613,996 alleles · very rare exomes 9/1,461,768 · genomes 0/152,228 · 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: MTPAP
Protein: p.Pro83Ser
Coding: c.247C>T
MANE Select: NM_018109
dbSNP: rs372003224
Type: single nucleotide variant
Location: chr10:30341551 (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

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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
MTPAP p.Arg76Gln Uncertain significance ★★ ⚠ same type
MTPAP p.Asn129Ser 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-pro83ser (accessed [today's date]).

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