Is ABCA3 p.Pro248Ser (c.742C>T) pathogenic?

ABCA3 p.Pro248Ser (c.742C>T) is classified Likely pathogenic in ABCA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely pathogenic (0.6424); Very rare (popmax 8.47e-05%, nfe); Associated with interstitial lung disease due to ABCA3 deficiency.

What condition is associated with ABCA3 p.Pro248Ser (c.742C>T)?

ABCA3 p.Pro248Ser (c.742C>T) is associated with interstitial lung disease due to ABCA3 deficiency (ClinVar).

How common is ABCA3 p.Pro248Ser (c.742C>T) in the general population?

ABCA3 p.Pro248Ser (c.742C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ABCA3 p.Pro248Ser (c.742C>T)?

AlphaMissense predicts likely pathogenic (score 0.6424) — an in-silico prediction, not a clinical call.

ABCA3 p.Pro248Ser

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.742C>T · VCV4525872

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6424 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

interstitial lung disease due to ABCA3 deficiency

Computational evidence

Protein change
AlphaMissense	0.6424	likely pathogenic ✓ concordant with ClinVar
REVEL	0.752	pathogenic-leaning
SaProt	LLR -10.43	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP -0.46, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 40 kb · p 0.47 · regional, not allelic
Overall
CADD	24.9	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 8.47e-05% European (non-Finnish) · 1/1,180,030 alleles

Overall 0.000657% 1/152,092 alleles · very rare

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.Pro248Ser
Coding: c.742C>T
MANE Select: NM_001089
Type: single nucleotide variant
Location: chr16:2319712 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB

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.Pro248Leu Pathogenic/Likely pathogenic ★★ same residue
ABCA3 p.Pro248= Likely benign ★ 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

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-pro248ser (accessed [today's date]).

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