Is SFTPC p.Ala149fs (c.444del) pathogenic?

SFTPC p.Ala149fs (c.444del) is classified Likely pathogenic in SFTPC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-01). No gnomAD frequency available for this variant; Associated with surfactant metabolism dysfunction, pulmonary, 2.

What condition is associated with SFTPC p.Ala149fs (c.444del)?

SFTPC p.Ala149fs (c.444del) is associated with surfactant metabolism dysfunction, pulmonary, 2 (ClinVar).

How common is SFTPC p.Ala149fs (c.444del) in the general population?

SFTPC p.Ala149fs (c.444del) is no gnomAD frequency available for this variant (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

SFTPC p.Ala149fs

c.444del · rs2131820994 · VCV1065347

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

surfactant metabolism dysfunction, pulmonary, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP -0.94, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: SFTPC
Protein: p.Ala149fs
Coding: c.444del
MANE Select: NM_001317778
dbSNP: rs2131820994
Type: Deletion
Location: chr8:22163907 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.71 · 3 PDB
Residue 149: a turn; the brichos domain

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

Disease context

surfactant metabolism dysfunction, pulmonary, 2 — 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

SFTPC p.Ala149Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
SFTPC p.Ala149Ser Uncertain significance ★ ⚠ same residue
SFTPC c.435+2T>C Pathogenic/Likely pathogenic ★★ same condition
SFTPC p.Ile73Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
SFTPC c.*193C>A Uncertain significance ★★ same condition
SFTPC p.Ile50Met Uncertain significance ★★ ⚠ same condition
SFTPC p.Leu45Pro Uncertain significance ★★ ⚠ same condition
SFTPC p.Val39Met 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/sftpc-p-ala149fs (accessed [today's date]).

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