Is SFTPB p.Asp355= (c.1065T>C) pathogenic?

SFTPB p.Asp355= (c.1065T>C) is classified Uncertain significance in SFTPB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Absent from gnomAD v4.1; Associated with surfactant metabolism dysfunction, pulmonary, 1.

What condition is associated with SFTPB p.Asp355= (c.1065T>C)?

SFTPB p.Asp355= (c.1065T>C) is associated with surfactant metabolism dysfunction, pulmonary, 1 (ClinVar).

How common is SFTPB p.Asp355= (c.1065T>C) in the general population?

SFTPB p.Asp355= (c.1065T>C) is absent from gnomAD v4.1 (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.Asp355=

c.1065T>C · rs1677332584 · VCV896603

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

surfactant metabolism dysfunction, pulmonary, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.259	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -2.4
Overall
CADD	2.279	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SFTPB
Protein: p.Asp355=
Coding: c.1065T>C
MANE Select: NM_000542
dbSNP: rs1677332584
Type: single nucleotide variant
Location: chr2:85662047 (GRCh38)
Gene constraint: LOEUF 0.846 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.31 · 9 PDB
Residue 355: the saposin b-type 3 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

For Neonatal acute respiratory distress syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

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.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.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-asp355 (accessed [today's date]).

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