Is ABCA12 p.Gln2149= (c.6447A>G) pathogenic?

ABCA12 p.Gln2149= (c.6447A>G) is classified Benign in ABCA12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). Very rare (popmax 0.00669%, eas).

How common is ABCA12 p.Gln2149= (c.6447A>G) in the general population?

ABCA12 p.Gln2149= (c.6447A>G) is very rare (popmax 0.00669%, eas) (gnomAD).

ABCA12 p.Gln2149=

c.6447A>G · rs147074166 · VCV2742116

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.84	acceptor gain · deltas
Pangolin	Δ0.49	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.052	GERP -4.8, phastCons 0.97
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,848 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.00353% 57/1,614,006 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.118%	846
East Asiangrpmax	0.00669%	14,949
Remaining individualsnot grpmax-eligible	0.0048%	20,835
Admixed American	0.00167%	60,006
European (non-Finnish)	0.00119%	84,284
South Asian	0.0011%	91,074

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ABCA12
Protein: p.Gln2149=
Coding: c.6447A>G
MANE Select: NM_173076
dbSNP: rs147074166
Type: single nucleotide variant
Location: chr2:214954054 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 2149: a UniProt-annotated variant site (in arci4b); a UniProt-annotated variant site (in arci4b; uncertain significance)

Full ABCA12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA12 p.Gln2149His Likely pathogenic ★ ⚠ same residue
ABCA12 c.2592+1G>A Likely pathogenic ★★ same type
ABCA12 c.5381+1G>C Pathogenic/Likely pathogenic ★★ same type
ABCA12 c.985+1G>A Likely pathogenic ★★ same type
ABCA12 p.Arg1297Ter Pathogenic ★★ same type
ABCA12 p.Arg1514Cys Pathogenic ★★ same type
ABCA12 p.Arg1514His Pathogenic/Likely pathogenic ★★ same type
ABCA12 p.Arg1515Ter Pathogenic ★★ 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/abca12-p-gln2149 (accessed [today's date]).

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