Is ABCA3 p.Val1648= (c.4944C>T) pathogenic?

ABCA3 p.Val1648= (c.4944C>T) is classified Conflicting classifications of pathogenicity in ABCA3 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-03-01). Rare (popmax 0.326%, nfe); Associated with hereditary pulmonary alveolar proteinosis.

What condition is associated with ABCA3 p.Val1648= (c.4944C>T)?

ABCA3 p.Val1648= (c.4944C>T) is associated with hereditary pulmonary alveolar proteinosis, interstitial lung disease due to ABCA3 deficiency (ClinVar).

How common is ABCA3 p.Val1648= (c.4944C>T) in the general population?

ABCA3 p.Val1648= (c.4944C>T) is rare (popmax 0.326%, nfe) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

ABCA3 p.Val1648=

c.4944C>T · rs142584479 · VCV787641

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.326%, nfe)

Conditions

hereditary pulmonary alveolar proteinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.021, phastCons 1
Overall
CADD	6.561	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.326% European (non-Finnish) · 3,845/1,180,016 alleles

Filtering AF 0.317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.314%

Overall 0.258% 4,168/1,613,170 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.326%	307
Remaining individualsnot grpmax-eligible	0.291%	343
Ashkenazi Jewishnot grpmax-eligible	0.145%	689
African / African-American	0.0626%	1,597
Admixed American	0.055%	1,819
South Asian	0.0176%	5,692
Finnishnot grpmax-eligible	0.00317%	31,526

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: ABCA3
Protein: p.Val1648=
Coding: c.4944C>T
MANE Select: NM_001089
dbSNP: rs142584479
Type: single nucleotide variant
Location: chr16:2277636 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 1648: a β-strand; a UniProt-annotated variant site (in smdp3)

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

Also linked: interstitial lung disease due to ABCA3 deficiency

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.1112-20G>A Likely pathogenic ★★ same condition
ABCA3 c.2053-1G>C Likely pathogenic ★★ same condition
ABCA3 c.2414+1G>A Likely pathogenic ★★ same condition
ABCA3 c.3863-98C>T Pathogenic ★★ same condition
ABCA3 c.614-2A>G Likely pathogenic ★★ same condition
ABCA3 p.Ala1070Thr Likely pathogenic ★★ ⚠ same condition
ABCA3 p.Arg1550Trp Likely pathogenic ★★ same condition
ABCA3 p.Arg155Trp 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-val1648 (accessed [today's date]).

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