Is MRAS p.Ala98Asp (c.293C>A) pathogenic?

MRAS p.Ala98Asp (c.293C>A) is classified Uncertain significance in MRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-31). AlphaMissense: likely pathogenic (0.5832); Very rare (popmax 0.0011%, sas).

How common is MRAS p.Ala98Asp (c.293C>A) in the general population?

MRAS p.Ala98Asp (c.293C>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about MRAS p.Ala98Asp (c.293C>A)?

AlphaMissense predicts likely pathogenic (score 0.5832) — an in-silico prediction, not a clinical call.

MRAS p.Ala98Asp

c.293C>A · rs2055261626 · VCV2991993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5832 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.5832	likely pathogenic
REVEL	0.305	indeterminate
SaProt	LLR -6.81	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.3	GERP 1.4, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 29 kb · p 1.4e-09 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,086 alleles

Overall 6.2e-05% 1/1,614,158 alleles · very rare exomes 1/1,461,860 · genomes 0/152,298 · 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.Ala98Asp
Coding: c.293C>A
MANE Select: NM_001085049
dbSNP: rs2055261626
Type: single nucleotide variant
Location: chr3:138397423 (GRCh38)
Gene constraint: LOEUF 0.444 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 86.61 · 11 PDB
Residue 98: an α-helix

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

Similar variants

MRAS p.Ala98Thr 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
MRAS p.Pro151= Benign ★★★ same type
MRAS p.Ala167Gly 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/mras-p-ala98asp (accessed [today's date]).

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