Is MRAS p.Thr95= (c.285T>C) pathogenic?

MRAS p.Thr95= (c.285T>C) is classified Likely benign in MRAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-24). Very rare (popmax 0.00801%, afr); Associated with Inborn genetic diseases.

What condition is associated with MRAS p.Thr95= (c.285T>C)?

MRAS p.Thr95= (c.285T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MRAS p.Thr95= (c.285T>C) in the general population?

MRAS p.Thr95= (c.285T>C) is very rare (popmax 0.00801%, afr) (gnomAD).

MRAS p.Thr95=

c.285T>C · rs776600463 · VCV1796946

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

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	all four deltas below 0.2 · T>A here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP -16	GERP -5
Overall
CADD	0.174	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,924 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000558% 9/1,614,034 alleles · very rare exomes 4/1,461,860 · genomes 5/152,174 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,487
European (non-Finnish)	0.000254%	393,340

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.Thr95=
Coding: c.285T>C
MANE Select: NM_001085049
dbSNP: rs776600463
Type: single nucleotide variant
Location: chr3:138397415 (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-thr95 (accessed [today's date]).

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