Is MRAS p.Val128= (c.384C>T) pathogenic?

MRAS p.Val128= (c.384C>T) is classified Likely benign in MRAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-04). Very rare (popmax 0.00669%, eas); Associated with Inborn genetic diseases.

What condition is associated with MRAS p.Val128= (c.384C>T)?

MRAS p.Val128= (c.384C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MRAS p.Val128= (c.384C>T) in the general population?

MRAS p.Val128= (c.384C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

MRAS p.Val128=

c.384C>T · rs770948545 · VCV1960590

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

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 -13	GERP -3.9
Overall
CADD	0.346	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,874 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000434% 7/1,613,916 alleles · very rare exomes 6/1,461,872 · genomes 1/152,044 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,958
Remaining individualsnot grpmax-eligible	0.0016%	62,490
South Asian	0.0011%	91,052
European (non-Finnish)	0.000169%	590,016

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.Val128=
Coding: c.384C>T
MANE Select: NM_001085049
dbSNP: rs770948545
Type: single nucleotide variant
Location: chr3:138398505 (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.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-val128 (accessed [today's date]).

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