Is NRAS p.Pro185= (c.555A>G) pathogenic?

NRAS p.Pro185= (c.555A>G) is classified Likely benign in NRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-11). Very rare (popmax 0.0011%, sas); Associated with RASopathy.

What condition is associated with NRAS p.Pro185= (c.555A>G)?

NRAS p.Pro185= (c.555A>G) is associated with RASopathy (ClinVar).

How common is NRAS p.Pro185= (c.555A>G) in the general population?

NRAS p.Pro185= (c.555A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

NRAS p.Pro185=

c.555A>G · rs761356631 · VCV2898768

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

RASopathy

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 -10	GERP -4.9
Overall
CADD	0.468	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,080 alleles

Overall 0.000186% 3/1,613,922 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
South Asiangrpmax	0.0011%	91,080
European (non-Finnish)	8.48e-05%	1,179,800

Ashkenazi Jewish 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: NRAS
Protein: p.Pro185=
Coding: c.555A>G
MANE Select: NM_002524
dbSNP: rs761356631
Type: single nucleotide variant
Location: chr1:114708550 (GRCh38)
Gene constraint: LOEUF 0.55 · pLI 0.94 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.56 · 36 PDB
Residue 185: the 'hypervariable region' region

Full NRAS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

RASopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NRAS p.Pro185Ser Uncertain significance ★★★ ⚠ same residue
NRAS p.Pro185Gln Uncertain significance ★ ⚠ same residue
NRAS p.Pro185Leu Uncertain significance ★ ⚠ same residue
NRAS p.Gly12Ser Pathogenic ★★★ same condition
NRAS p.Gly60Glu Pathogenic ★★★ same condition
NRAS p.Ile24Asn Likely pathogenic ★★★ same condition
NRAS p.Thr50Ile Pathogenic ★★★ ⚠ same condition
NRAS p.Thr58Ile Pathogenic ★★★ 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/nras-p-pro185 (accessed [today's date]).

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