Is ABCC6 p.Arg264Gln (c.791G>A) pathogenic?

ABCC6 p.Arg264Gln (c.791G>A) is classified Uncertain significance in ABCC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). AlphaMissense: likely benign (0.0652); Very rare (popmax 0.00669%, eas); Associated with pseudoxanthoma elasticum, forme fruste.

What condition is associated with ABCC6 p.Arg264Gln (c.791G>A)?

ABCC6 p.Arg264Gln (c.791G>A) is associated with pseudoxanthoma elasticum, forme fruste, autosomal recessive inherited pseudoxanthoma elasticum, arterial calcification, generalized, of infancy, 2 (ClinVar).

How common is ABCC6 p.Arg264Gln (c.791G>A) in the general population?

ABCC6 p.Arg264Gln (c.791G>A) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about ABCC6 p.Arg264Gln (c.791G>A)?

AlphaMissense predicts likely benign (score 0.0652) — an in-silico prediction, not a clinical call.

ABCC6 p.Arg264Gln

c.791G>A · VCV3578610

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0652 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

pseudoxanthoma elasticum, forme fruste

Computational evidence

Protein change
AlphaMissense	0.0652	likely benign
REVEL	0.376	indeterminate
SaProt	LLR -5.62	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 -2.7	GERP -2.4
Regional constraint	o/e 0.98	unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic
Overall
CADD	0.342	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 0.00669% East Asian · 3/44,850 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00192% 31/1,613,314 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,950
African / African-American	0.00667%	14,991
Remaining individualsnot grpmax-eligible	0.0032%	31,235
South Asian	0.0022%	45,524
Admixed American	0.00167%	59,970
European (non-Finnish)	0.00153%	65,524

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: ABCC6
Protein: p.Arg264Gln
Coding: c.791G>A
MANE Select: NM_001171
Type: single nucleotide variant
Location: chr16:16208731 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB

Full ABCC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pseudoxanthoma elasticum, forme fruste — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive inherited pseudoxanthoma elasticum arterial calcification, generalized, of infancy, 2

Similar variants

ABCC6 p.Arg264= Uncertain significance ★ same residue
ABCC6 p.Arg264Trp Uncertain significance ★★ ⚠ same residue
ABCC6 c.1868-5T>G Pathogenic/Likely pathogenic ★★ same condition
ABCC6 c.2591-1G>T Likely pathogenic ★★ same condition
ABCC6 c.2787+1G>T Pathogenic ★★ same condition
ABCC6 c.3507-1G>A Pathogenic ★★ same condition
ABCC6 c.37-1G>A Pathogenic ★★ same condition
ABCC6 c.3736-1G>A Pathogenic ★★ same condition

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/abcc6-p-arg264gln (accessed [today's date]).

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