Is ABCC12 p.Lys894Met (c.2681A>T) pathogenic?

ABCC12 p.Lys894Met (c.2681A>T) is classified Benign in ABCC12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1176); Common (popmax 8.22%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ABCC12 p.Lys894Met (c.2681A>T)?

AlphaMissense predicts likely benign (score 0.1176) — an in-silico prediction, not a clinical call.

ABCC12 p.Lys894Met

Q: How common is ABCC12 p.Lys894Met (c.2681A>T) in the general population?

ABCC12 p.Lys894Met (c.2681A>T) is common (popmax 8.22%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2681A>T · rs8057474 · VCV784623

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1176 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.22%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1176	likely benign
REVEL	0.314	indeterminate
SaProt	LLR -6.74	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.82	GERP -2.3
Regional constraint	o/e 0.97	unconstrained · MANE · 63 kb · p 0.2 · regional, not allelic
Overall
CADD	11.43	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 8.22% African / African-American · 6,172/75,050 alleles

Filtering AF 8.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.98%

Overall 0.502% 8,102/1,614,126 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.22%	12
Middle Eastern	1.39%	72
Ashkenazi Jewishnot grpmax-eligible	0.996%	100
Remaining individualsnot grpmax-eligible	0.803%	125
Admixed American	0.757%	132
European (non-Finnish)	0.0481%	2,081
South Asian	0.0285%	3,503
East Asian	0.00223%	44,888
Finnishnot grpmax-eligible	0.00156%	64,028

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.Lys894Met
Coding: c.2681A>T
MANE Select: NM_001393797
dbSNP: rs8057474
Type: single nucleotide variant
Location: chr16:48104361 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.09
Residue 894: the abc transmembrane type-1 2 domain; a UniProt-annotated variant site (in)

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

Similar variants

ABCC12 p.Thr1080Ala Uncertain significance ★★ ⚠ same type
ABCC12 p.Arg122= Likely benign ★★ same type
ABCC12 p.Gln831Ter Likely benign ★★ same type
ABCC12 p.Glu1191Ala Benign ★★ same type
ABCC12 p.Gly164Ter Benign/Likely benign ★★ same type
ABCC12 p.Lys1344= Benign ★★ same type
ABCC12 p.Phe54= Benign ★★ same type
ABCC12 p.Ala1312Thr Uncertain significance ★ ⚠ 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/abcc12-p-lys894met (accessed [today's date]).

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