Is MPV17 p.Pro98Gln (c.293C>A) pathogenic?

MPV17 p.Pro98Gln (c.293C>A) is classified Likely pathogenic in MPV17 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-06). AlphaMissense: likely pathogenic (0.9573); Very rare (popmax 0.00267%, afr).

How common is MPV17 p.Pro98Gln (c.293C>A) in the general population?

MPV17 p.Pro98Gln (c.293C>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about MPV17 p.Pro98Gln (c.293C>A)?

AlphaMissense predicts likely pathogenic (score 0.9573) — an in-silico prediction, not a clinical call.

MPV17 p.Pro98Gln

c.293C>A · rs267607258 · VCV2888969

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9573 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9573	likely pathogenic ✓ concordant with ClinVar · top 10% in MPV17
REVEL	0.838	moderately pathogenic-leaning
SaProt	LLR -14.89	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	28.5	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 0.00267% African / African-American · 2/74,920 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,968 alleles · very rare exomes 0/1,461,784 · genomes 2/152,184 · 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: MPV17
Protein: p.Pro98Gln
Coding: c.293C>A
MANE Select: NM_002437
dbSNP: rs267607258
Type: single nucleotide variant
Location: chr2:27312576 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.23
Residue 98: a UniProt-annotated variant site (in mtdps6); a UniProt-annotated variant site (in mtdps6 and cmt2ee; results in incomplete closing of the channel)

Full MPV17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MPV17 p.Pro98Leu Pathogenic/Likely pathogenic ★★ same residue
MPV17 p.Pro98= Likely benign ★ same residue
MPV17 p.Pro98fs Pathogenic ★★ same residue
MPV17 c.186+2T>C Pathogenic/Likely pathogenic ★★ same type
MPV17 c.279+1G>T Pathogenic ★★ same type
MPV17 c.375+1G>A Likely pathogenic ★★ same type
MPV17 c.375+1G>T Likely pathogenic ★★ same type
MPV17 c.375+2T>C Likely pathogenic ★★ 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/mpv17-p-pro98gln (accessed [today's date]).

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