Is MRAS p.Phe38= (c.114T>C) pathogenic?

MRAS p.Phe38= (c.114T>C) is classified Likely benign in MRAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-06). Very rare (popmax 8.62e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MRAS p.Phe38= (c.114T>C)?

MRAS p.Phe38= (c.114T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MRAS p.Phe38= (c.114T>C) in the general population?

MRAS p.Phe38= (c.114T>C) is very rare (popmax 8.62e-05%, nfe) (gnomAD).

MRAS p.Phe38=

c.114T>C · rs747697719 · VCV2871575

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.62e-05%, nfe)

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 -0.13	GERP 0.1, phastCons 0.81
Overall
CADD	9.071	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.62e-05% European (non-Finnish) · 1/1,160,018 alleles

Overall 0.000128% 2/1,568,240 alleles · very rare exomes 2/1,415,962 · genomes 0/152,278 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00165%	60,632
European (non-Finnish)grpmax	8.62e-05%	1,160,017

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe38=
Coding: c.114T>C
MANE Select: NM_001085049
dbSNP: rs747697719
Type: single nucleotide variant
Location: chr3:138372997 (GRCh38)
Gene constraint: LOEUF 0.444 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 86.61 · 11 PDB
Residue 38: a binding site

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-phe38 (accessed [today's date]).

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