Is MRAS p.Ser75= (c.225C>T) pathogenic?

MRAS p.Ser75= (c.225C>T) is classified Likely benign in MRAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-18). Ultra-rare (popmax 0.0121%, sas); Associated with Inborn genetic diseases.

What condition is associated with MRAS p.Ser75= (c.225C>T)?

MRAS p.Ser75= (c.225C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MRAS p.Ser75= (c.225C>T) in the general population?

MRAS p.Ser75= (c.225C>T) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

MRAS p.Ser75=

c.225C>T · rs563066079 · VCV1547407

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

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 -6	GERP -4.7
Overall
CADD	10.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% South Asian · 11/91,080 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.00136% 22/1,614,070 alleles · ultra-rare exomes 18/1,461,778 · genomes 4/152,292 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,280
East Asian	0.00446%	22,437
African / African-American	0.004%	25,015
Admixed American	0.00333%	30,007
European (non-Finnish)	0.000339%	294,996

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.Ser75=
Coding: c.225C>T
MANE Select: NM_001085049
dbSNP: rs563066079
Type: single nucleotide variant
Location: chr3:138397355 (GRCh38)
Gene constraint: LOEUF 0.444 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 86.61 · 11 PDB
Residue 75: an α-helix

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-ser75 (accessed [today's date]).

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