Is MRAS p.Ser4= (c.12C>T) pathogenic?

MRAS p.Ser4= (c.12C>T) is classified Likely benign in MRAS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-05). Ultra-rare (popmax 0.0443%, afr); Associated with Inborn genetic diseases.

What condition is associated with MRAS p.Ser4= (c.12C>T)?

MRAS p.Ser4= (c.12C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MRAS p.Ser4= (c.12C>T) in the general population?

MRAS p.Ser4= (c.12C>T) is ultra-rare (popmax 0.0443%, afr) (gnomAD).

MRAS p.Ser4=

c.12C>T · rs35056274 · VCV1427167

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0443%, afr)

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 -0.4	GERP 3.2, phastCons 0.04
Overall
CADD	12.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0443% African / African-American · 31/70,054 alleles

Filtering AF 0.032% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0278%

Overall 0.0022% 34/1,542,940 alleles · ultra-rare exomes 15/1,390,616 · genomes 19/152,324 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0443%	2,260
Remaining individualsnot grpmax-eligible	0.00336%	29,723
European (non-Finnish)	8.67e-05%	1,152,794

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.Ser4=
Coding: c.12C>T
MANE Select: NM_001085049
dbSNP: rs35056274
Type: single nucleotide variant
Location: chr3:138372895 (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-ser4 (accessed [today's date]).

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