Is ABCC12 p.Lys66fs (c.197_198del) pathogenic?

ABCC12 p.Lys66fs (c.197198del) is classified Benign in ABCC12 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Low-frequency (popmax 4.85%, afr).

How common is ABCC12 p.Lys66fs (c.197_198del) in the general population?

ABCC12 p.Lys66fs (c.197_198del) is low-frequency (popmax 4.85%, afr) (gnomAD).

ABCC12 p.Lys66fs

c.197_198del · rs148156488 · VCV781323

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 4.85%, afr)

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 4 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.79	GERP -2
Overall
CADD	17.16	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 4.85% African / African-American · 3,636/75,024 alleles

Filtering AF 4.71% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.66%

Overall 0.261% 4,213/1,614,194 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.85%	21
Remaining individualsnot grpmax-eligible	0.402%	249
Admixed American	0.353%	283
Middle Eastern	0.313%	319
Ashkenazi Jewishnot grpmax-eligible	0.0405%	2,467
South Asian	0.0154%	6,506
European (non-Finnish)	0.00585%	17,102

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: ABCC12
Protein: p.Lys66fs
Coding: c.197_198del
MANE Select: NM_001393797
dbSNP: rs148156488
Type: Deletion
Location: chr16:48143987 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.09

Full ABCC12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/abcc12-p-lys66fs (accessed [today's date]).

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