Is ABCA3 p.Leu101Pro (c.302T>C) pathogenic?

ABCA3 p.Leu101Pro (c.302T>C) is classified Pathogenic in ABCA3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2004-03-25). AlphaMissense: likely pathogenic (0.6724); Absent from gnomAD v4.1; Associated with interstitial lung disease due to ABCA3 deficiency.

What condition is associated with ABCA3 p.Leu101Pro (c.302T>C)?

ABCA3 p.Leu101Pro (c.302T>C) is associated with interstitial lung disease due to ABCA3 deficiency (ClinVar).

How common is ABCA3 p.Leu101Pro (c.302T>C) in the general population?

ABCA3 p.Leu101Pro (c.302T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCA3 p.Leu101Pro (c.302T>C)?

AlphaMissense predicts likely pathogenic (score 0.6724) — an in-silico prediction, not a clinical call.

ABCA3 p.Leu101Pro

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.302T>C · rs121909182 · VCV8012

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6724 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

interstitial lung disease due to ABCA3 deficiency

Computational evidence

Protein change
AlphaMissense	0.6724	likely pathogenic ✓ concordant with ClinVar
REVEL	0.669	pathogenic-leaning
SaProt	LLR -9.79	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 40 kb · p 0.47 · regional, not allelic
Overall
CADD	23.6	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: ABCA3
Protein: p.Leu101Pro
Coding: c.302T>C
MANE Select: NM_001089
dbSNP: rs121909182
Type: single nucleotide variant
Location: chr16:2326027 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 101: a UniProt-annotated variant site (in smdp3; loss of intracellular vesicle membrane location; loss of proteolytic cleavage; does not affect n-glycosylation; loss of atp hydrolysis activity; decreases atp binding in vitro)

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

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

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

ABCA3 p.Leu101Phe Uncertain significance ★ ⚠ same residue
ABCA3 c.1112-20G>A 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-leu101pro (accessed [today's date]).

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