Is MTPAP p.Arg71Ter (c.211C>T) pathogenic?

MTPAP p.Arg71Ter (c.211C>T) is classified Uncertain significance in MTPAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). Very rare (popmax 0.00133%, afr).

How common is MTPAP p.Arg71Ter (c.211C>T) in the general population?

MTPAP p.Arg71Ter (c.211C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

MTPAP p.Arg71Ter

c.211C>T · rs2538469599 · VCV3233611

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -0.33, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,016 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,614,036 alleles · very rare exomes 3/1,461,782 · genomes 0/152,254 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,016
European (non-Finnish)	0.000169%	589,995

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.Arg71Ter
Coding: c.211C>T
MANE Select: NM_018109
dbSNP: rs2538469599
Type: single nucleotide variant
Location: chr10:30341587 (GRCh38)
Gene constraint: LOEUF 0.641 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 83.16 · 1 PDB
Residue 71: an α-helix

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

Similar variants

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
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-arg71ter (accessed [today's date]).

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