Is MRAS p.Val91Ile (c.271G>A) pathogenic?

MRAS p.Val91Ile (c.271G>A) is classified Uncertain significance in MRAS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-06-13). AlphaMissense: ambiguous (0.3765); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with MRAS p.Val91Ile (c.271G>A)?

MRAS p.Val91Ile (c.271G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MRAS p.Val91Ile (c.271G>A) in the general population?

MRAS p.Val91Ile (c.271G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about MRAS p.Val91Ile (c.271G>A)?

AlphaMissense predicts ambiguous (score 0.3765) — an in-silico prediction, not a clinical call.

MRAS p.Val91Ile

c.271G>A · rs2055260842 · VCV1795174

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3765 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3765	ambiguous
REVEL	0.66	pathogenic-leaning
SaProt	LLR -8.98	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 29 kb · p 1.4e-09 · regional, not allelic
Overall
CADD	32.0	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 0.00133% African / African-American · 1/74,908 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,614,002 alleles · very rare exomes 5/1,461,858 · genomes 1/152,144 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,908
European (non-Finnish)	0.000424%	236,005

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.Val91Ile
Coding: c.271G>A
MANE Select: NM_001085049
dbSNP: rs2055260842
Type: single nucleotide variant
Location: chr3:138397401 (GRCh38)
Gene constraint: LOEUF 0.444 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 86.61 · 11 PDB
Residue 91: a β-strand

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.Val91= Likely benign ★ same residue
MRAS p.Val91Ala Uncertain significance ★ ⚠ same residue
MRAS p.Val91Leu 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

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-val91ile (accessed [today's date]).

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