Is CSF2RA p.Ala131= (c.393G>A) pathogenic?

CSF2RA p.Ala131= (c.393G>A) is classified Benign in CSF2RA (ClinVar, Single submitter, 3 submitters; last evaluated 2026-01-23). Rare (popmax 0.221%, afr); Associated with surfactant metabolism dysfunction, pulmonary, 4.

What condition is associated with CSF2RA p.Ala131= (c.393G>A)?

CSF2RA p.Ala131= (c.393G>A) is associated with surfactant metabolism dysfunction, pulmonary, 4 (ClinVar).

How common is CSF2RA p.Ala131= (c.393G>A) in the general population?

CSF2RA p.Ala131= (c.393G>A) is rare (popmax 0.221%, afr) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

CSF2RA p.Ala131=

c.393G>A · rs143104828 · VCV1170895

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.221%, afr)

Conditions

surfactant metabolism dysfunction, pulmonary, 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.60	acceptor gain · deltas
Pangolin	Δ0.44	gain · loss 0.27 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -8	GERP 1
Overall
CADD	9.859	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.221% African / African-American · 166/75,026 alleles

Filtering AF 0.194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.183%

Overall 0.0151% 243/1,613,914 alleles · rare exomes 138/1,461,668 · genomes 105/152,246 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.221%	452
Remaining individualsnot grpmax-eligible	0.0368%	2,717
East Asian	0.029%	3,452
Admixed American	0.0217%	4,613
South Asian	0.00769%	13,011
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
European (non-Finnish)	0.0017%	58,994

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.Ala131=
Coding: c.393G>A
MANE Select: NM_172245
dbSNP: rs143104828
Type: single nucleotide variant
Location: chrX:1288808 (GRCh38)
Structure: AlphaFold pLDDT 82.15 · 2 PDB
Residue 131: a turn

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.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
CSF2RA p.Leu336Val 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-ala131 (accessed [today's date]).

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