Is SFTPB p.Asp281= (c.843C>T) pathogenic?

SFTPB p.Asp281= (c.843C>T) is classified Benign in SFTPB (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-23). Common (popmax 24.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary pulmonary alveolar proteinosis.

What condition is associated with SFTPB p.Asp281= (c.843C>T)?

SFTPB p.Asp281= (c.843C>T) is associated with hereditary pulmonary alveolar proteinosis, surfactant metabolism dysfunction, pulmonary, 1 (ClinVar).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

SFTPB p.Asp281=

Q: How common is SFTPB p.Asp281= (c.843C>T) in the general population?

SFTPB p.Asp281= (c.843C>T) is common (popmax 24.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.843C>T · rs3024810 · VCV165202

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 24.3%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hereditary pulmonary alveolar proteinosis

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 -5.4	GERP -3.6
Overall
CADD	0.198	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 24.3% African / African-American · 18,211/74,964 alleles

Filtering AF 24% ClinGen BA1/BS1 input FAF95, joint · FAF99 23.9%

Overall 1.31% 21,188/1,612,084 alleles · common exomes 10,634/1,459,828 · genomes 10,554/152,256 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	24.3%	4
Admixed American	1.71%	59
Remaining individualsnot grpmax-eligible	1.67%	60
Middle Eastern	1.14%	88
Ashkenazi Jewishnot grpmax-eligible	0.301%	332
South Asian	0.0651%	1,536
European (non-Finnish)	0.0588%	1,699
Finnishnot grpmax-eligible	0.00314%	31,846
East Asian	0.00223%	44,822

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.Asp281=
Coding: c.843C>T
MANE Select: NM_000542
dbSNP: rs3024810
Type: single nucleotide variant
Location: chr2:85663677 (GRCh38)
Gene constraint: LOEUF 0.846 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.31 · 9 PDB
Residue 281: 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 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
SFTPB p.Arg276Trp 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-asp281 (accessed [today's date]).

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