Is SFTPC p.Val8= (c.24C>G) pathogenic?

SFTPC p.Val8= (c.24C>G) is classified Benign/Likely benign in SFTPC (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-10-14). Ultra-rare (popmax 0.0403%, nfe); Associated with surfactant metabolism dysfunction, pulmonary, 2.

What condition is associated with SFTPC p.Val8= (c.24C>G)?

SFTPC p.Val8= (c.24C>G) is associated with surfactant metabolism dysfunction, pulmonary, 2, hereditary pulmonary alveolar proteinosis (ClinVar).

How common is SFTPC p.Val8= (c.24C>G) in the general population?

SFTPC p.Val8= (c.24C>G) is ultra-rare (popmax 0.0403%, nfe) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

SFTPC p.Val8=

c.24C>G · rs144603526 · VCV362550

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0403%, nfe)

Conditions

surfactant metabolism dysfunction, pulmonary, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.46 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.8	GERP -0.84, phastCons 0.97
Overall
CADD	9.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0403% European (non-Finnish) · 476/1,180,004 alleles

Filtering AF 0.0373% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0361%

Overall 0.0886% 1,430/1,614,032 alleles · ultra-rare exomes 1,309/1,461,780 · genomes 121/152,252 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.72%	37
Remaining individualsnot grpmax-eligible	0.19%	525
European (non-Finnish)grpmax	0.0403%	2,479
Admixed American	0.0333%	3,001
Middle Eastern	0.0165%	6,062
African / African-American	0.00933%	10,719
Finnishnot grpmax-eligible	0.00156%	63,940

Ashkenazi Jewish 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.Val8=
Coding: c.24C>G
MANE Select: NM_001317778
dbSNP: rs144603526
Type: single nucleotide variant
Location: chr8:22161852 (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

Disease context

surfactant metabolism dysfunction, pulmonary, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary pulmonary alveolar proteinosis

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.Val8Leu Uncertain significance ★ ⚠ same residue
SFTPC p.Val8Phe Uncertain significance ★ ⚠ same residue
SFTPC c.435+2T>C Pathogenic/Likely pathogenic ★★ same condition
SFTPC p.Ile73Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
SFTPC p.Leu110Pro 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

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-val8 (accessed [today's date]).

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