Is SFTPC p.Val39fs (c.115del) pathogenic?

SFTPC p.Val39fs (c.115del) is classified Uncertain significance in SFTPC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-16). Very rare (popmax 0.000339%, nfe).

How common is SFTPC p.Val39fs (c.115del) in the general population?

SFTPC p.Val39fs (c.115del) is very rare (popmax 0.000339%, nfe) (gnomAD).

SFTPC p.Val39fs

c.115del · VCV3369268

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

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 2 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.1	GERP -1.1, phastCons 0.001
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(GTG)n simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,964 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,962 alleles · very rare exomes 4/1,461,790 · genomes 1/152,172 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)grpmax	0.000339%	294,991

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SFTPC
Protein: p.Val39fs
Coding: c.115del
MANE Select: NM_001317778
Type: Deletion
Location: chr8:22162646 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.71 · 3 PDB

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

Similar variants

SFTPC p.Val39Met Uncertain significance ★★ ⚠ same residue
SFTPC p.Val39Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
SFTPC p.Ala149fs Likely pathogenic ★ same type
SFTPC p.Glu135fs Pathogenic ★ same type
SFTPC p.His142fs Likely pathogenic ★ same type
SFTPC c.43-21_43-18del Likely benign ★ same type

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-val39fs (accessed [today's date]).

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