Is SFTPB p.Pro351Ser (c.1051C>T) pathogenic?

SFTPB p.Pro351Ser (c.1051C>T) is classified Likely benign in SFTPB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-17). AlphaMissense: likely benign (0.0611); No allele count reported in gnomAD v4.1 (AN 1,603,446); Associated with hereditary pulmonary alveolar proteinosis.

What condition is associated with SFTPB p.Pro351Ser (c.1051C>T)?

SFTPB p.Pro351Ser (c.1051C>T) is associated with hereditary pulmonary alveolar proteinosis (ClinVar).

How common is SFTPB p.Pro351Ser (c.1051C>T) in the general population?

SFTPB p.Pro351Ser (c.1051C>T) is no allele count reported in gnomAD v4.1 (AN 1,603,446) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

What do computational predictors say about SFTPB p.Pro351Ser (c.1051C>T)?

AlphaMissense predicts likely benign (score 0.0611) — an in-silico prediction, not a clinical call.

SFTPB p.Pro351Ser

c.1051C>T · rs2466661561 · VCV2385366

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0611 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,603,446)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary pulmonary alveolar proteinosis

Computational evidence

Protein change
AlphaMissense	0.0611	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -6.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -4.2, phastCons 0.091
Regional constraint	o/e 0.88	unconstrained · MANE · 6,707 bp · p 0.0066 · regional, not allelic
Overall
CADD	0.058	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,603,446). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SFTPB
Protein: p.Pro351Ser
Coding: c.1051C>T
MANE Select: NM_000542
dbSNP: rs2466661561
Type: single nucleotide variant
Location: chr2:85662061 (GRCh38)
Gene constraint: LOEUF 0.846 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.31 · 9 PDB
Residue 351: the saposin b-type 3 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

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-pro351ser (accessed [today's date]).

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