Is ABCC12 p.Arg911His (c.2732G>A) pathogenic?

ABCC12 p.Arg911His (c.2732G>A) is classified Uncertain significance in ABCC12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.128); Very rare (popmax 0.00266%, afr).

How common is ABCC12 p.Arg911His (c.2732G>A) in the general population?

ABCC12 p.Arg911His (c.2732G>A) is very rare (popmax 0.00266%, afr) (gnomAD).

What do computational predictors say about ABCC12 p.Arg911His (c.2732G>A)?

AlphaMissense predicts likely benign (score 0.128) — an in-silico prediction, not a clinical call.

ABCC12 p.Arg911His

c.2732G>A · VCV4636170

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.128 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00266%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.128	likely benign
REVEL	0.802	moderately pathogenic-leaning
SaProt	LLR -12.31	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.22	GERP 0.89, phastCons 0.009
Regional constraint	o/e 0.97	unconstrained · MANE · 63 kb · p 0.2 · regional, not allelic
Overall
CADD	23.2	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 0.00266% African / African-American · 2/75,058 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.00103% 15/1,461,884 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00266%	37,529
East Asian	0.00223%	44,886
Finnishnot grpmax-eligible	0.00156%	64,032
European (non-Finnish)	0.000932%	107,277

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.Arg911His
Coding: c.2732G>A
MANE Select: NM_001393797
Type: single nucleotide variant
Location: chr16:48104310 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.09
Residue 911: the abc transmembrane type-1 2 domain

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

Similar variants

ABCC12 p.Arg911Ser Uncertain significance ★ ⚠ same residue
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

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-arg911his (accessed [today's date]).

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