Is MPV17 p.Arg40Ser (c.120G>T) pathogenic?

MPV17 p.Arg40Ser (c.120G>T) is classified Uncertain significance in MPV17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.2593); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with MPV17 p.Arg40Ser (c.120G>T)?

MPV17 p.Arg40Ser (c.120G>T) is associated with Inborn genetic diseases (ClinVar).

How common is MPV17 p.Arg40Ser (c.120G>T) in the general population?

MPV17 p.Arg40Ser (c.120G>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about MPV17 p.Arg40Ser (c.120G>T)?

AlphaMissense predicts likely benign (score 0.2593) — an in-silico prediction, not a clinical call.

MPV17 p.Arg40Ser

c.120G>T · VCV4109979

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2593 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2593	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -9.47	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.048	GERP -4.7, phastCons 0.15
Regional constraint	o/e 0.92	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	18.7	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 0.00534% African / African-American · 4/74,934 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,614,092 alleles · very rare exomes 3/1,461,884 · genomes 1/152,208 · 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.Arg40Ser
Coding: c.120G>T
MANE Select: NM_002437
Type: single nucleotide variant
Location: chr2:27313060 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MPV17 p.Arg40Trp Uncertain significance ★ ⚠ same residue
MPV17 p.Ala12Val Uncertain significance ★★ ⚠ same condition
MPV17 p.Arg175Trp Uncertain significance ★★ ⚠ same condition
MPV17 p.Leu176Pro Uncertain significance ★★ ⚠ same condition
MPV17 p.Tyr136Cys Uncertain significance ★★ ⚠ same condition
MPV17 p.Ala121Val Uncertain significance ★ ⚠ same condition
MPV17 p.Ala13Asp Uncertain significance ★ ⚠ same condition
MPV17 p.Ala13Thr 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/mpv17-p-arg40ser (accessed [today's date]).

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