Is MRAP p.Met1Val (c.1A>G) pathogenic?

MRAP p.Met1Val (c.1A>G) is classified Pathogenic in MRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-30). Very rare (popmax 0.000509%, nfe); Associated with glucocorticoid deficiency 1.

What condition is associated with MRAP p.Met1Val (c.1A>G)?

MRAP p.Met1Val (c.1A>G) is associated with glucocorticoid deficiency 1 (ClinVar).

How common is MRAP p.Met1Val (c.1A>G) in the general population?

MRAP p.Met1Val (c.1A>G) is very rare (popmax 0.000509%, nfe) (gnomAD).

How is Familial glucocorticoid deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MRAP p.Met1Val

c.1A>G · rs1555897462 · VCV444067

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Conditions

glucocorticoid deficiency 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.722	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Overall
CADD	20.6	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 0.000509% European (non-Finnish) · 6/1,178,212 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000411% 6/1,459,782 alleles · very rare

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.Met1Val
Coding: c.1A>G
MANE Select: NM_001379228
dbSNP: rs1555897462
Type: single nucleotide variant
Location: chr21:32298972 (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

glucocorticoid deficiency 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial glucocorticoid deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Ireland)

Similar variants

MRAP p.Met1Ile Pathogenic ★★ same residue
MRAP c.106+1del Pathogenic ★★ same condition
MRAP c.106+1G>C Pathogenic ★★ same type
MRAP c.*108A>G Benign ★★ same type
MRAP p.Thr130Ile Benign ★★ same type
MRAP c.106+1G>A Pathogenic ★ same type
MRAP c.106+15G>C Uncertain significance ★ same type
MRAP c.-151+125C>T Uncertain significance ★ 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-met1val (accessed [today's date]).

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