Is MRAS p.Asp64= (c.192C>T) pathogenic?

MRAS p.Asp64= (c.192C>T) is classified Conflicting classifications of pathogenicity in MRAS (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-12). Very rare (popmax 0.00816%, eas); Associated with Inborn genetic diseases.

What condition is associated with MRAS p.Asp64= (c.192C>T)?

MRAS p.Asp64= (c.192C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MRAS p.Asp64= (c.192C>T) in the general population?

MRAS p.Asp64= (c.192C>T) is very rare (popmax 0.00816%, eas) (gnomAD).

MRAS p.Asp64=

c.192C>T · rs373753637 · VCV1782840

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00816%, eas)

Conditions

Inborn genetic diseases

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 -7.1	GERP -7.2
Overall
CADD	1.359	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00816% East Asian · 3/36,764 alleles

Filtering AF 0.00284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00251%

Overall 0.00327% 48/1,466,612 alleles · very rare exomes 47/1,314,464 · genomes 1/152,148 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00816%	12,255
European (non-Finnish)	0.00379%	26,402
Finnishnot grpmax-eligible	0.00325%	30,812
Remaining individualsnot grpmax-eligible	0.00178%	56,258

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.Asp64=
Coding: c.192C>T
MANE Select: NM_001085049
dbSNP: rs373753637
Type: single nucleotide variant
Location: chr3:138373075 (GRCh38)
Gene constraint: LOEUF 0.444 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 86.61 · 11 PDB
Residue 64: 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.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
MRAS p.Glu117Gly 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-asp64 (accessed [today's date]).

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