Is SFTPC p.Ala83Val (c.248C>T) pathogenic?

SFTPC p.Ala83Val (c.248C>T) is classified Uncertain significance in SFTPC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.1307); Absent from gnomAD v4.1; Associated with hereditary pulmonary alveolar proteinosis.

What condition is associated with SFTPC p.Ala83Val (c.248C>T)?

SFTPC p.Ala83Val (c.248C>T) is associated with hereditary pulmonary alveolar proteinosis (ClinVar).

How common is SFTPC p.Ala83Val (c.248C>T) in the general population?

SFTPC p.Ala83Val (c.248C>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.Ala83Val (c.248C>T)?

AlphaMissense predicts likely benign (score 0.1307) — an in-silico prediction, not a clinical call.

SFTPC p.Ala83Val

c.248C>T · VCV3953172

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1307 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary pulmonary alveolar proteinosis

Computational evidence

Protein change
AlphaMissense	0.1307	likely benign
REVEL	0.752	pathogenic-leaning
SaProt	LLR -6.83	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.6, phastCons 0.99
Regional constraint	o/e 0.87	unconstrained · MANE · 2,209 bp · p 0.036 · regional, not allelic
Overall
CADD	22.5	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.Ala83Val
Coding: c.248C>T
MANE Select: NM_001317778
Type: single nucleotide variant
Location: chr8:22163126 (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

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

SFTPC p.Ala83Thr Uncertain significance ★ ⚠ same residue
SFTPC p.Ile73Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
SFTPC p.Leu110Pro Pathogenic/Likely pathogenic ★★ same condition
SFTPC p.Ile50Met Uncertain significance ★★ ⚠ same condition
SFTPC c.43-7G>A Benign/Likely benign ★★ same condition
SFTPC c.435+12T>G Benign/Likely benign ★★ same condition
SFTPC c.435+15G>A Benign/Likely benign ★★ same condition
SFTPC c.*12T>A Benign/Likely benign ★★ 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-ala83val (accessed [today's date]).

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