Is SFTPB p.Ser197= (c.591C>T) pathogenic?

SFTPB p.Ser197= (c.591C>T) is classified Benign/Likely benign in SFTPB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-13). Rare (popmax 0.249%, afr); Associated with hereditary pulmonary alveolar proteinosis.

What condition is associated with SFTPB p.Ser197= (c.591C>T)?

SFTPB p.Ser197= (c.591C>T) is associated with hereditary pulmonary alveolar proteinosis (ClinVar).

How common is SFTPB p.Ser197= (c.591C>T) in the general population?

SFTPB p.Ser197= (c.591C>T) is rare (popmax 0.249%, afr) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

SFTPB p.Ser197=

c.591C>T · rs45530632 · VCV725729

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.249%, afr)

Conditions

hereditary pulmonary alveolar proteinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.22	acceptor gain · deltas
Pangolin	Δ0.31	loss · gain 0.15 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP -10	GERP -2.8
Overall
CADD	2.061	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.249% African / African-American · 187/75,040 alleles

Filtering AF 0.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.209%

Overall 0.0147% 237/1,613,752 alleles · rare exomes 127/1,461,462 · genomes 110/152,290 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.249%	401
Remaining individualsnot grpmax-eligible	0.0304%	3,288
Admixed American	0.0167%	6,002
Middle Eastern	0.0165%	6,062
South Asian	0.00769%	13,011
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
European (non-Finnish)	0.00102%	98,308

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.Ser197=
Coding: c.591C>T
MANE Select: NM_000542
dbSNP: rs45530632
Type: single nucleotide variant
Location: chr2:85665370 (GRCh38)
Gene constraint: LOEUF 0.846 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.31 · 9 PDB

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

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.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
SFTPB p.Asp118Asn Uncertain significance ★★ ⚠ same condition
SFTPB p.Asp158His Uncertain significance ★★ ⚠ same condition
SFTPB p.Asp380Asn 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-ser197 (accessed [today's date]).

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