Is RAF1 p.Gln192= (c.576A>G) pathogenic?

RAF1 p.Gln192= (c.576A>G) is classified Benign/Likely benign in RAF1 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-01-17). Ultra-rare (popmax 0.0357%, nfe); Associated with Noonan syndrome and Noonan-related syndrome.

What condition is associated with RAF1 p.Gln192= (c.576A>G)?

RAF1 p.Gln192= (c.576A>G) is associated with Noonan syndrome and Noonan-related syndrome, RASopathy (ClinVar).

How common is RAF1 p.Gln192= (c.576A>G) in the general population?

RAF1 p.Gln192= (c.576A>G) is ultra-rare (popmax 0.0357%, nfe) (gnomAD).

RAF1 p.Gln192=

c.576A>G · rs148759910 · VCV40597

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, nfe)

Conditions

Noonan syndrome and Noonan-related syndrome

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 -2.2	GERP -5.5
Overall
CADD	1.841	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0357% European (non-Finnish) · 421/1,179,932 alleles

Filtering AF 0.0328% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0317%

Overall 0.0275% 444/1,613,856 alleles · ultra-rare exomes 421/1,461,756 · genomes 23/152,100 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0357%	2,803
Remaining individualsnot grpmax-eligible	0.0176%	5,680
Middle Eastern	0.0164%	6,084
Admixed American	0.00833%	12,001
African / African-American	0.00267%	37,438
East Asian	0.00223%	44,880
South Asian	0.0022%	45,543
Finnishnot grpmax-eligible	0.00156%	64,004

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: RAF1
Protein: p.Gln192=
Coding: c.576A>G
MANE Select: NM_002880
dbSNP: rs148759910
Type: single nucleotide variant
Location: chr3:12608771 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.24 · 76 PDB

Full RAF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Noonan syndrome and Noonan-related syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: RASopathy

Similar variants

RAF1 p.Gln192His Uncertain significance ★ same residue
RAF1 p.Arg256Ser Likely pathogenic ★★★ ⚠ same condition
RAF1 p.Gly361Ala Pathogenic ★★★ ⚠ same condition
RAF1 p.Leu613Val Pathogenic ★★★ same condition
RAF1 p.Pro261Ser Pathogenic ★★★ ⚠ same condition
RAF1 p.Ser257Leu Pathogenic ★★★ ⚠ same condition
RAF1 p.Ser257Pro Likely pathogenic ★★★ ⚠ same condition
RAF1 p.Ser259Ala 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/raf1-p-gln192 (accessed [today's date]).

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