Is ABCC12 p.Ile414Val (c.1240A>G) pathogenic?

ABCC12 p.Ile414Val (c.1240A>G) is classified Uncertain significance in ABCC12 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-21). AlphaMissense: likely benign (0.1469); Absent from gnomAD v4.1.

How common is ABCC12 p.Ile414Val (c.1240A>G) in the general population?

ABCC12 p.Ile414Val (c.1240A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC12 p.Ile414Val (c.1240A>G)?

AlphaMissense predicts likely benign (score 0.1469) — an in-silico prediction, not a clinical call.

ABCC12 p.Ile414Val

c.1240A>G · rs2543652860 · VCV2296108

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1469 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1469	likely benign
REVEL	0.415	indeterminate
SaProt	LLR -6.72	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 4.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 63 kb · p 0.2 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCC12
Protein: p.Ile414Val
Coding: c.1240A>G
MANE Select: NM_001393797
dbSNP: rs2543652860
Type: single nucleotide variant
Location: chr16:48128734 (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

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.Lys894Met Benign ★★ same type
ABCC12 p.Phe54= Benign ★★ 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-ile414val (accessed [today's date]).

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