Is MPV17 p.His152= (c.456T>C) pathogenic?

MPV17 p.His152= (c.456T>C) is classified Likely benign in MPV17 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-08). Very rare (popmax 0.00134%, afr).

How common is MPV17 p.His152= (c.456T>C) in the general population?

MPV17 p.His152= (c.456T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

MPV17 p.His152=

c.456T>C · rs1242291564 · VCV1641209

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.034	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 1, phastCons 1
Overall
CADD	7.502	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,888 alleles

Overall 0.00031% 5/1,613,628 alleles · very rare exomes 4/1,461,506 · genomes 1/152,122 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,616
African / African-Americangrpmax	0.00134%	74,888

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.His152=
Coding: c.456T>C
MANE Select: NM_002437
dbSNP: rs1242291564
Type: single nucleotide variant
Location: chr2:27311904 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.23
Residue 152: a UniProt-annotated variant site (in mtdps6)

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

Similar variants

MPV17 p.His152Tyr 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
MPV17 c.376-2A>C 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-his152 (accessed [today's date]).

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