Is ABCA12 p.Val247fs (c.740_743del) pathogenic?

ABCA12 p.Val247fs (c.740743del) is classified Pathogenic in ABCA12 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-01). Very rare (popmax 0.00329%, sas).

How common is ABCA12 p.Val247fs (c.740_743del) in the general population?

ABCA12 p.Val247fs (c.740_743del) is very rare (popmax 0.00329%, sas) (gnomAD).

ABCA12 p.Val247fs

c.740_743del · rs2469406811 · VCV2807855

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

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 7 of 53
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.61	GERP -4.3

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,068 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000411% 6/1,461,444 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,356
European (non-Finnish)	0.000254%	393,264

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.Val247fs
Coding: c.740_743del
MANE Select: NM_173076
dbSNP: rs2469406811
Type: Deletion
Location: chr2:215045966 (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-val247fs (accessed [today's date]).

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