Is ABCA12 p.Ser177fs (c.529del) pathogenic?

ABCA12 p.Ser177fs (c.529del) is classified Pathogenic in ABCA12 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-26). Very rare (popmax 8.48e-05%, nfe).

How common is ABCA12 p.Ser177fs (c.529del) in the general population?

ABCA12 p.Ser177fs (c.529del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

ABCA12 p.Ser177fs

c.529del · rs1701282121 · VCV2734386

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 53
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.7	GERP 2.8, phastCons 1
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,596 alleles

Overall 0.000657% 1/152,162 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: ABCA12
Protein: p.Ser177fs
Coding: c.529del
MANE Select: NM_173076
dbSNP: rs1701282121
Type: Deletion
Location: chr2:215049790 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32

Full ABCA12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA12 p.Asn528fs Pathogenic/Likely pathogenic ★★ same type
ABCA12 p.Ile1128fs Pathogenic/Likely pathogenic ★★ same type
ABCA12 p.Phe2286fs Pathogenic ★★ same type
ABCA12 p.Val2442fs Pathogenic ★★ same type
ABCA12 c.2683+2del Likely pathogenic ★ same type
ABCA12 c.5469_5472del Pathogenic ★ same type
ABCA12 c.6962+2del Likely pathogenic ★ same type
ABCA12 c.7541_7542+1del Likely pathogenic ★ same type

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/abca12-p-ser177fs (accessed [today's date]).

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