Is MRAS p.Ala5= (c.15C>T) pathogenic?

MRAS p.Ala5= (c.15C>T) is classified Likely benign in MRAS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-30). Ultra-rare (popmax 0.022%, amr); Associated with Inborn genetic diseases.

What condition is associated with MRAS p.Ala5= (c.15C>T)?

MRAS p.Ala5= (c.15C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MRAS p.Ala5= (c.15C>T) in the general population?

MRAS p.Ala5= (c.15C>T) is ultra-rare (popmax 0.022%, amr) (gnomAD).

MRAS p.Ala5=

c.15C>T · rs752887551 · VCV1539564

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.022%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -10
Overall
CADD	2.261	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.022% Admixed American · 10/45,426 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00907%

Overall 0.00369% 57/1,544,096 alleles · ultra-rare exomes 46/1,391,878 · genomes 11/152,218 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.022%	4,543
East Asian	0.0104%	9,635
Remaining individualsnot grpmax-eligible	0.00672%	14,872
Finnishnot grpmax-eligible	0.00472%	21,171
African / African-American	0.00429%	23,323
European (non-Finnish)	0.00286%	34,949

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: MRAS
Protein: p.Ala5=
Coding: c.15C>T
MANE Select: NM_001085049
dbSNP: rs752887551
Type: single nucleotide variant
Location: chr3:138372898 (GRCh38)
Gene constraint: LOEUF 0.444 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 86.61 · 11 PDB

Full MRAS 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

MRAS p.Ala5Thr Uncertain significance ★★ ⚠ same residue
MRAS p.Ala167Gly Uncertain significance ★★ ⚠ same condition
MRAS p.Arg105Cys Uncertain significance ★★ ⚠ same condition
MRAS p.Arg193Gln Uncertain significance ★★ ⚠ same condition
MRAS p.Asn10Ser Uncertain significance ★★ ⚠ same condition
MRAS p.Asn126Lys Uncertain significance ★★ ⚠ same condition
MRAS p.Asn126Ser Uncertain significance ★★ ⚠ same condition
MRAS p.Gln178Lys 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/mras-p-ala5 (accessed [today's date]).

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