Is ABCA3 p.Ala149Val (c.446C>T) pathogenic?

ABCA3 p.Ala149Val (c.446C>T) is classified Conflicting classifications of pathogenicity in ABCA3 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-11-11). AlphaMissense: likely benign (0.0993); Rare (popmax 0.302%, mid); Associated with interstitial lung disease due to ABCA3 deficiency.

What condition is associated with ABCA3 p.Ala149Val (c.446C>T)?

ABCA3 p.Ala149Val (c.446C>T) is associated with interstitial lung disease due to ABCA3 deficiency, hereditary pulmonary alveolar proteinosis (ClinVar).

How common is ABCA3 p.Ala149Val (c.446C>T) in the general population?

ABCA3 p.Ala149Val (c.446C>T) is rare (popmax 0.302%, mid) (gnomAD).

What do computational predictors say about ABCA3 p.Ala149Val (c.446C>T)?

AlphaMissense predicts likely benign (score 0.0993) — an in-silico prediction, not a clinical call.

ABCA3 p.Ala149Val

Q: How is Interstitial lung disease due to ABCA3 deficiency inherited?

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

c.446C>T · rs145483014 · VCV816671

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0993 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.302%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

interstitial lung disease due to ABCA3 deficiency

Computational evidence

Protein change
AlphaMissense	0.0993	likely benign
REVEL	0.386	indeterminate
SaProt	LLR -5.95	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -0.66, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 40 kb · p 0.47 · regional, not allelic
Overall
CADD	23.8	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

Grpmax group 0.302% Middle Eastern · 18/5,958 alleles

Filtering AF 0.195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.161%

Overall 0.0118% 189/1,595,790 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.302%	331
Ashkenazi Jewishnot grpmax-eligible	0.126%	791
Admixed American	0.0309%	3,235
Remaining individualsnot grpmax-eligible	0.0258%	3,878
African / African-American	0.012%	8,319
South Asian	0.0112%	8,925
European (non-Finnish)	0.0068%	14,699
Finnishnot grpmax-eligible	0.00182%	54,814

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.Ala149Val
Coding: c.446C>T
MANE Select: NM_001089
dbSNP: rs145483014
Type: single nucleotide variant
Location: chr16:2324405 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 149: a β-strand

Full ABCA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

interstitial lung disease due to ABCA3 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary pulmonary alveolar proteinosis

For Interstitial lung disease due to ABCA3 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

ABCA3 p.Ala149Thr Uncertain significance ★ ⚠ same residue
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

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-ala149val (accessed [today's date]).

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