Is CSF2RA p.Arg164Gln (c.491G>A) pathogenic?

CSF2RA p.Arg164Gln (c.491G>A) is classified Benign/Likely benign in CSF2RA (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Rare (popmax 0.944%, nfe); Associated with surfactant metabolism dysfunction, pulmonary, 4.

What condition is associated with CSF2RA p.Arg164Gln (c.491G>A)?

CSF2RA p.Arg164Gln (c.491G>A) is associated with surfactant metabolism dysfunction, pulmonary, 4 (ClinVar).

How common is CSF2RA p.Arg164Gln (c.491G>A) in the general population?

CSF2RA p.Arg164Gln (c.491G>A) is rare (popmax 0.944%, nfe) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CSF2RA p.Arg164Gln

c.491G>A · rs138964358 · VCV163003

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.944%, nfe)

Conditions

surfactant metabolism dysfunction, pulmonary, 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.13	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.46	GERP -0.044
Regional constraint	o/e 1.06	unconstrained · MANE · 27 kb · p 0.2 · regional, not allelic
Overall
CADD	0.186	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.944% European (non-Finnish) · 11,134/1,179,294 alleles

Filtering AF 0.929% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.923%

Overall 0.776% 12,514/1,613,084 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	3.62%	28
European (non-Finnish)grpmax	0.944%	106
Ashkenazi Jewishnot grpmax-eligible	0.855%	117
Remaining individualsnot grpmax-eligible	0.682%	147
Admixed American	0.369%	271
Finnishnot grpmax-eligible	0.264%	378
African / African-American	0.171%	586
Middle Eastern	0.165%	605
South Asian	0.148%	674
East Asian	0.0111%	8,976

Amish 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: CSF2RA
Protein: p.Arg164Gln
Coding: c.491G>A
MANE Select: NM_172245 · reported on NM_001161529
dbSNP: rs138964358
Type: single nucleotide variant
Location: chrX:1290354 (GRCh38)
Structure: AlphaFold pLDDT 82.15 · 2 PDB

Full CSF2RA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

surfactant metabolism dysfunction, pulmonary, 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary pulmonary alveolar proteinosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Elderly, Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

CSF2RA p.Arg164Trp Uncertain significance ★ same residue
CSF2RA p.Arg199Ter Pathogenic ★★ same condition
CSF2RA p.Arg217Ter Pathogenic/Likely pathogenic ★★ same condition
CSF2RA p.Gln204Ter Pathogenic ★★ same condition
CSF2RA p.Gln263Ter Pathogenic/Likely pathogenic ★★ same condition
CSF2RA p.Arg354Gln Uncertain significance ★★ same condition
CSF2RA p.Gly339Val Uncertain significance ★★ same condition
CSF2RA p.Gly386Arg 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/csf2ra-p-arg164gln (accessed [today's date]).

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