Is SFTPC p.Asp105Val (c.314A>T) pathogenic?

SFTPC p.Asp105Val (c.314A>T) is classified Likely pathogenic in SFTPC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-03). AlphaMissense: likely pathogenic (0.8086); Absent from gnomAD v4.1; Associated with surfactant metabolism dysfunction, pulmonary, 2.

What condition is associated with SFTPC p.Asp105Val (c.314A>T)?

SFTPC p.Asp105Val (c.314A>T) is associated with surfactant metabolism dysfunction, pulmonary, 2 (ClinVar).

How common is SFTPC p.Asp105Val (c.314A>T) in the general population?

SFTPC p.Asp105Val (c.314A>T) is absent from gnomAD v4.1 (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 SFTPC p.Asp105Val (c.314A>T)?

AlphaMissense predicts likely pathogenic (score 0.8086) — an in-silico prediction, not a clinical call.

SFTPC p.Asp105Val

c.314A>T · rs2131817329 · VCV1333368

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8086 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

surfactant metabolism dysfunction, pulmonary, 2

Computational evidence

Protein change
AlphaMissense	0.8086	likely pathogenic ✓ concordant with ClinVar · top 8% in SFTPC
REVEL	0.95	strongly pathogenic-leaning
SaProt	LLR -15.73	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 2,209 bp · p 0.036 · regional, not allelic
Overall
CADD	27.2	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

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: SFTPC
Protein: p.Asp105Val
Coding: c.314A>T
MANE Select: NM_001317778
dbSNP: rs2131817329
Type: single nucleotide variant
Location: chr8:22163192 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.71 · 3 PDB
Residue 105: a β-strand; 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.Asp105Gly Likely pathogenic ★ same residue
SFTPC p.Asp105Tyr Pathogenic ★ 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-asp105val (accessed [today's date]).

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