Is ABCC12 p.Arg69Gln (c.206G>A) pathogenic?

ABCC12 p.Arg69Gln (c.206G>A) is classified Uncertain significance in ABCC12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). AlphaMissense: likely benign (0.0733); Ultra-rare (popmax 0.0668%, afr).

How common is ABCC12 p.Arg69Gln (c.206G>A) in the general population?

ABCC12 p.Arg69Gln (c.206G>A) is ultra-rare (popmax 0.0668%, afr) (gnomAD).

What do computational predictors say about ABCC12 p.Arg69Gln (c.206G>A)?

AlphaMissense predicts likely benign (score 0.0733) — an in-silico prediction, not a clinical call.

ABCC12 p.Arg69Gln

c.206G>A · VCV3872015

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0733 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0668%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0733	likely benign
REVEL	0.226	benign-leaning
SaProt	LLR -7.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.43	GERP -4.1, phastCons 0.004
Regional constraint	o/e 0.97	unconstrained · MANE · 63 kb · p 0.2 · regional, not allelic
Overall
CADD	1.636	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

Grpmax group 0.0668% African / African-American · 50/74,866 alleles

Filtering AF 0.052% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0468%

Overall 0.00632% 102/1,614,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0668%	1,497
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0096%	10,418
Admixed American	0.005%	20,007
East Asian	0.00446%	22,439
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Finnishnot grpmax-eligible	0.00312%	32,021
European (non-Finnish)	0.00305%	32,779
South Asian	0.0011%	91,078

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.Arg69Gln
Coding: c.206G>A
MANE Select: NM_001393797
Type: single nucleotide variant
Location: chr16:48143979 (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-arg69gln (accessed [today's date]).

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