Is MRAP p.Ser79fs (c.235del) pathogenic?

MRAP p.Ser79fs (c.235del) is classified Uncertain significance in MRAP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-18). Ultra-rare (popmax 0.0107%, afr); Associated with MRAP-related disorder.

What condition is associated with MRAP p.Ser79fs (c.235del)?

MRAP p.Ser79fs (c.235del) is associated with MRAP-related disorder (ClinVar).

How common is MRAP p.Ser79fs (c.235del) in the general population?

MRAP p.Ser79fs (c.235del) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

MRAP p.Ser79fs

c.235del · VCV3355327

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Conditions

MRAP-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.43	GERP -2.2
Overall
CADD	0.964	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 0.0107% African / African-American · 8/74,956 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000558% 9/1,614,124 alleles · ultra-rare exomes 4/1,461,866 · genomes 5/152,258 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,370
Admixed American	0.00167%	60,014

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: MRAP
Protein: p.Ser79fs
Coding: c.235del
MANE Select: NM_001379228 · reported on NM_206898
Type: Deletion
Location: chr21:32314578 (GRCh38)
Gene constraint: LOEUF 1.44 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.50 · 1 PDB

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

Disease context

MRAP-related disorder

Similar variants

MRAP c.106+1G>A Pathogenic ★ same condition
MRAP c.106+2dup Pathogenic ★ same condition
MRAP p.Asp27= Likely benign same condition
MRAP c.106+1del Pathogenic ★★ same type
MRAP c.207delG Uncertain significance ★ same type
MRAP p.Asn6fs 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/mrap-p-ser79fs (accessed [today's date]).

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