Is MRAS p.Arg105= (c.315C>T) pathogenic?

MRAS p.Arg105= (c.315C>T) is classified Likely benign in MRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-29). Very rare (popmax 0.00133%, afr).

How common is MRAS p.Arg105= (c.315C>T) in the general population?

MRAS p.Arg105= (c.315C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

MRAS p.Arg105=

c.315C>T · VCV3674548

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.35	GERP -1.9, phastCons 0.99
Overall
CADD	10.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,922 alleles

Overall 6.2e-05% 1/1,614,030 alleles · very rare exomes 0/1,461,838 · genomes 1/152,192 · joint denominator

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.Arg105=
Coding: c.315C>T
MANE Select: NM_001085049
Type: single nucleotide variant
Location: chr3:138397445 (GRCh38)
Gene constraint: LOEUF 0.444 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 86.61 · 11 PDB
Residue 105: an α-helix

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

Similar variants

MRAS p.Arg105Cys Uncertain significance ★★ ⚠ same residue
MRAS p.Arg105Gly Uncertain significance ★ ⚠ same residue
MRAS p.Arg105His Uncertain significance ★ ⚠ same residue
MRAS p.Gln71Arg Likely pathogenic ★★★ same type
MRAS p.Gly23Arg Likely pathogenic ★★★ same type
MRAS p.Gly23Val Likely pathogenic ★★★ same type
MRAS p.Thr68Ile Likely pathogenic ★★★ same type
MRAS p.Gln59= Benign ★★★ 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/mras-p-arg105 (accessed [today's date]).

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