Is ABCA3 p.Ser598Phe (c.1793C>T) pathogenic?

ABCA3 p.Ser598Phe (c.1793C>T) is classified Uncertain significance in ABCA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). AlphaMissense: likely benign (0.2209); Absent from gnomAD v4.1; Associated with hereditary pulmonary alveolar proteinosis.

What condition is associated with ABCA3 p.Ser598Phe (c.1793C>T)?

ABCA3 p.Ser598Phe (c.1793C>T) is associated with hereditary pulmonary alveolar proteinosis (ClinVar).

How common is ABCA3 p.Ser598Phe (c.1793C>T) in the general population?

ABCA3 p.Ser598Phe (c.1793C>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 ABCA3 p.Ser598Phe (c.1793C>T)?

AlphaMissense predicts likely benign (score 0.2209) — an in-silico prediction, not a clinical call.

ABCA3 p.Ser598Phe

c.1793C>T · VCV3849948

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2209 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary pulmonary alveolar proteinosis

Computational evidence

Protein change
AlphaMissense	0.2209	likely benign
REVEL	0.531	indeterminate
SaProt	LLR -8.71	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.22	acceptor loss, 32 bp away · masked 0 · deltas
Pangolin	Δ0.38	gain · loss 0.00 · SpliceAI calls loss · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 40 kb · p 0.47 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: ABCA3
Protein: p.Ser598Phe
Coding: c.1793C>T
MANE Select: NM_001089
Type: single nucleotide variant
Location: chr16:2298489 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 598: a turn; the abc transporter 1 domain

Full ABCA3 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

ABCA3 c.2053-1G>C Likely pathogenic ★★ same condition
ABCA3 c.3863-98C>T Pathogenic ★★ same condition
ABCA3 p.Arg1550Trp Likely pathogenic ★★ same condition
ABCA3 p.Arg43Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCA3 p.Arg43His Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCA3 p.Glu1540Lys Likely pathogenic ★★ same condition
ABCA3 p.Glu292Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCA3 p.Gly1459Asp Likely pathogenic ★★ 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/abca3-p-ser598phe (accessed [today's date]).

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