Is MAPRE2 p.Ser28Ter (c.83C>G) pathogenic?

MAPRE2 p.Ser28Ter (c.83C>G) is classified Uncertain significance in MAPRE2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-27). Ultra-rare (popmax 0.0167%, mid); Associated with Inborn genetic diseases.

What condition is associated with MAPRE2 p.Ser28Ter (c.83C>G)?

MAPRE2 p.Ser28Ter (c.83C>G) is associated with Inborn genetic diseases (ClinVar).

How common is MAPRE2 p.Ser28Ter (c.83C>G) in the general population?

MAPRE2 p.Ser28Ter (c.83C>G) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

MAPRE2 p.Ser28Ter

c.83C>G · rs909396421 · VCV2394791

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.8, phastCons 1
Overall
CADD	17.15	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Middle Eastern · 1/5,988 alleles

Filtering AF 0.00371% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00333%

Overall 0.0039% 60/1,540,218 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,988
European (non-Finnish)	0.00474%	21,099
African / African-American	0.00412%	24,274
Remaining individualsnot grpmax-eligible	0.00335%	29,845

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: MAPRE2
Protein: p.Ser28Ter
Coding: c.83C>G
MANE Select: NM_014268 · reported on NM_001143827
dbSNP: rs909396421
Type: single nucleotide variant
Location: chr18:35005550 (GRCh38)
Gene constraint: LOEUF 0.494 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 75.12

Full MAPRE2 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

MAPRE2 p.Glu318Lys Uncertain significance ★★ ⚠ same condition
MAPRE2 c.123-6T>C Uncertain significance ★ same condition
MAPRE2 p.Arg143His Uncertain significance ★ ⚠ same condition
MAPRE2 p.Arg220Gln Uncertain significance ★ ⚠ same condition
MAPRE2 p.Gln174Glu Uncertain significance ★ ⚠ same condition
MAPRE2 p.Gln291Arg Uncertain significance ★ ⚠ same condition
MAPRE2 p.Glu309Val Uncertain significance ★ ⚠ same condition
MAPRE2 p.His317Gln 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/mapre2-p-ser28ter (accessed [today's date]).

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