Is MPV17 p.Ala13Pro (c.37G>C) pathogenic?

MPV17 p.Ala13Pro (c.37G>C) is classified Uncertain significance in MPV17 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-01). AlphaMissense: likely pathogenic (0.5746); Very rare (popmax 0.000254%, nfe).

How common is MPV17 p.Ala13Pro (c.37G>C) in the general population?

MPV17 p.Ala13Pro (c.37G>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about MPV17 p.Ala13Pro (c.37G>C)?

AlphaMissense predicts likely pathogenic (score 0.5746) — an in-silico prediction, not a clinical call.

MPV17 p.Ala13Pro

c.37G>C · rs1679896510 · VCV2578847

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5746 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.5746	likely pathogenic
REVEL	0.578	indeterminate
SaProt	LLR -14.33	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.21	GERP -0.77, phastCons 0.009
Regional constraint	o/e 0.92	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	18.27	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000254% European (non-Finnish) · 3/1,180,030 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,034 alleles · very rare exomes 3/1,461,668 · genomes 0/152,366 · 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.Ala13Pro
Coding: c.37G>C
MANE Select: NM_002437
dbSNP: rs1679896510
Type: single nucleotide variant
Location: chr2:27322481 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.23

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

Similar variants

MPV17 p.Ala13Asp Uncertain significance ★ ⚠ same residue
MPV17 p.Ala13Thr Uncertain significance ★ ⚠ 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
MPV17 c.376-1G>A Pathogenic/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-ala13pro (accessed [today's date]).

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