Is SFTPB p.Glu97= (c.291G>A) pathogenic?

SFTPB p.Glu97= (c.291G>A) is classified Benign/Likely benign in SFTPB (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-27). Low-frequency (popmax 2.84%, mid); Associated with surfactant metabolism dysfunction, pulmonary, 1.

What condition is associated with SFTPB p.Glu97= (c.291G>A)?

SFTPB p.Glu97= (c.291G>A) is associated with surfactant metabolism dysfunction, pulmonary, 1, hereditary pulmonary alveolar proteinosis (ClinVar).

How common is SFTPB p.Glu97= (c.291G>A) in the general population?

SFTPB p.Glu97= (c.291G>A) is low-frequency (popmax 2.84%, mid) (gnomAD).

How is Neonatal acute respiratory distress syndrome inherited?

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

SFTPB p.Glu97=

c.291G>A · rs34682912 · VCV165205

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.84%, mid)

Conditions

surfactant metabolism dysfunction, pulmonary, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.033	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.96	GERP -3.2
Overall
CADD	1.796	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.84% Middle Eastern · 172/6,060 alleles

Filtering AF 2.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.36%

Overall 0.295% 4,762/1,613,860 alleles · low-frequency exomes 4,345/1,461,680 · genomes 417/152,180 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.84%	35
Ashkenazi Jewishnot grpmax-eligible	1.85%	54
South Asian	0.769%	130
Remaining individualsnot grpmax-eligible	0.522%	192
Admixed American	0.255%	392
European (non-Finnish)	0.235%	426
African / African-American	0.096%	1,042
Finnishnot grpmax-eligible	0.0328%	3,047
East Asian	0.00446%	22,432

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.Glu97=
Coding: c.291G>A
MANE Select: NM_000542
dbSNP: rs34682912
Type: single nucleotide variant
Location: chr2:85666719 (GRCh38)
Gene constraint: LOEUF 0.846 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.31 · 9 PDB
Residue 97: the saposin b-type 1 domain

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

Disease context

surfactant metabolism dysfunction, pulmonary, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary pulmonary alveolar proteinosis

For Neonatal acute respiratory distress syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

SFTPB p.Glu97Gly Uncertain significance ★ ⚠ 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-glu97 (accessed [today's date]).

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