Is MPZL2 p.Pro86Ser (c.256C>T) pathogenic?

MPZL2 p.Pro86Ser (c.256C>T) is classified Uncertain significance in MPZL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: likely pathogenic (0.6113); Very rare (popmax 0.00449%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MPZL2 p.Pro86Ser (c.256C>T)?

MPZL2 p.Pro86Ser (c.256C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MPZL2 p.Pro86Ser (c.256C>T) in the general population?

MPZL2 p.Pro86Ser (c.256C>T) is very rare (popmax 0.00449%, nfe) (gnomAD).

What do computational predictors say about MPZL2 p.Pro86Ser (c.256C>T)?

AlphaMissense predicts likely pathogenic (score 0.6113) — an in-silico prediction, not a clinical call.

MPZL2 p.Pro86Ser

c.256C>T · rs145098802 · VCV2515193

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6113 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00449%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6113	likely pathogenic
REVEL	0.356	indeterminate
SaProt	LLR -9.56	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.8	GERP 1.1, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 6,900 bp · p 0.079 · regional, not allelic
Overall
CADD	23.7	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 0.00449% European (non-Finnish) · 53/1,180,032 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00359% 58/1,613,922 alleles · very rare exomes 52/1,461,710 · genomes 6/152,212 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00449%	22,265
Finnishnot grpmax-eligible	0.00312%	32,012
African / African-American	0.00267%	37,461
Remaining individualsnot grpmax-eligible	0.0016%	62,474

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: MPZL2
Protein: p.Pro86Ser
Coding: c.256C>T
MANE Select: NM_005797
dbSNP: rs145098802
Type: single nucleotide variant
Location: chr11:118262618 (GRCh38)
Gene constraint: LOEUF 1.703 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.54
Residue 86: a UniProt-annotated variant site (in dfnb111; pathogenic); the ig-like v-type domain

Full MPZL2 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

MPZL2 p.Pro129Arg Likely pathogenic ★★ same condition
MPZL2 p.Arg103Gln Uncertain significance ★★ ⚠ same condition
MPZL2 p.Arg33Gln Uncertain significance ★★ ⚠ same condition
MPZL2 p.Ile151Thr Uncertain significance ★★ same condition
MPZL2 p.Arg147Cys Uncertain significance ★ ⚠ same condition
MPZL2 p.Arg147His Uncertain significance ★ ⚠ same condition
MPZL2 p.Arg179Trp Uncertain significance ★ ⚠ same condition
MPZL2 p.Arg182Gln 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/mpzl2-p-pro86ser (accessed [today's date]).

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