Is MAPRE2 p.Arg143Cys (c.427C>T) pathogenic?

MAPRE2 p.Arg143Cys (c.427C>T) is classified Pathogenic/Likely pathogenic in MAPRE2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-09-26). AlphaMissense: likely pathogenic (0.9935); Absent from gnomAD v4.1; Associated with Developmental disorder.

What condition is associated with MAPRE2 p.Arg143Cys (c.427C>T)?

MAPRE2 p.Arg143Cys (c.427C>T) is associated with Developmental disorder, skin creases, congenital symmetric circumferential, 2 (ClinVar).

How common is MAPRE2 p.Arg143Cys (c.427C>T) in the general population?

MAPRE2 p.Arg143Cys (c.427C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPRE2 p.Arg143Cys (c.427C>T)?

AlphaMissense predicts likely pathogenic (score 0.9935) — an in-silico prediction, not a clinical call.

MAPRE2 p.Arg143Cys

c.427C>T · rs864309720 · VCV218930

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9935 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,974)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Developmental disorder

Computational evidence

Protein change
AlphaMissense	0.9935	likely pathogenic ✓ concordant with ClinVar
REVEL	0.352	indeterminate
SaProt	LLR -13.66	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.2, phastCons 1
Regional constraint	o/e 0.26	constrained · MANE · 61 kb · p 5.4e-31 · regional, not allelic
Overall
CADD	33.0	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

No allele count reported in gnomAD v4.1 (AN 1,608,974). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MAPRE2
Protein: p.Arg143Cys
Coding: c.427C>T
MANE Select: NM_014268
dbSNP: rs864309720
Type: single nucleotide variant
Location: chr18:35101976 (GRCh38)
Gene constraint: LOEUF 0.494 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 75.12
Residue 143: the calponin-homology (ch) domain; a UniProt-annotated variant site (in cscsc2; enhances binding to microtubules)

Full MAPRE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Developmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: skin creases, congenital symmetric circumferential, 2

Similar variants

MAPRE2 p.Arg143His Uncertain significance ★ ⚠ same residue
MAPRE2 p.Arg173Gln Likely pathogenic ★ same condition
MAPRE2 p.Ala123Thr Uncertain significance ★ same condition
MAPRE2 p.Arg127Gln Uncertain significance ★ ⚠ same condition
MAPRE2 p.Arg173Ter Conflicting classifications of pathogenicity ★ ⚠ same condition
MAPRE2 p.Gly24Arg Uncertain significance ★ ⚠ same condition
MAPRE2 p.Tyr158Cys Uncertain significance ★ ⚠ same condition
MAPRE2 p.Val290Met Conflicting classifications of pathogenicity ★ ⚠ 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/mapre2-p-arg143cys (accessed [today's date]).

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