Is SFTPB p.Arg236= (c.708C>T) pathogenic?

SFTPB p.Arg236= (c.708C>T) is classified Benign/Likely benign in SFTPB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-07-06). Rare (popmax 0.808%, sas); Associated with hereditary pulmonary alveolar proteinosis.

What condition is associated with SFTPB p.Arg236= (c.708C>T)?

SFTPB p.Arg236= (c.708C>T) is associated with hereditary pulmonary alveolar proteinosis, surfactant metabolism dysfunction, pulmonary, 1 (ClinVar).

How common is SFTPB p.Arg236= (c.708C>T) in the general population?

SFTPB p.Arg236= (c.708C>T) is rare (popmax 0.808%, sas) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

SFTPB p.Arg236=

c.708C>T · rs367661082 · VCV227073

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.808%, sas)

Conditions

hereditary pulmonary alveolar proteinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.53	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP -0.36, phastCons 0.027
Overall
CADD	9.092	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.808% South Asian · 720/89,124 alleles

Filtering AF 0.759% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.739%

Overall 0.0589% 942/1,599,064 alleles · rare exomes 866/1,446,732 · genomes 76/152,332 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.808%	124
East Asian	0.337%	297
Remaining individualsnot grpmax-eligible	0.0872%	1,146
African / African-American	0.012%	8,311
Admixed American	0.00171%	58,338
European (non-Finnish)	0.000766%	130,523

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: SFTPB
Protein: p.Arg236=
Coding: c.708C>T
MANE Select: NM_000542
dbSNP: rs367661082
Type: single nucleotide variant
Location: chr2:85663812 (GRCh38)
Gene constraint: LOEUF 0.846 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.31 · 9 PDB
Residue 236: a UniProt-annotated variant site (in smdp1); the saposin b-type 2 domain

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

Disease context

hereditary pulmonary alveolar proteinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: surfactant metabolism dysfunction, pulmonary, 1

For Hereditary pulmonary alveolar proteinosis (Orphanet):

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

Similar variants

SFTPB p.Arg236Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
SFTPB c.195+1G>A Pathogenic/Likely pathogenic ★★ same condition
SFTPB c.582+5G>A Uncertain significance ★★ same condition
SFTPB c.*922G>A Uncertain significance ★★ same condition
SFTPB p.Ala184Pro Uncertain significance ★★ ⚠ same condition
SFTPB p.Arg165Gln Uncertain significance ★★ ⚠ same condition
SFTPB p.Arg217Gln Uncertain significance ★★ ⚠ same condition
SFTPB p.Arg276Gln 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/sftpb-p-arg236 (accessed [today's date]).

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