Is ABCC6 p.Glu699Gln (c.2095G>C) pathogenic?

ABCC6 p.Glu699Gln (c.2095G>C) is classified Uncertain significance in ABCC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-19). AlphaMissense: likely benign (0.1538); Absent from gnomAD v4.1.

How common is ABCC6 p.Glu699Gln (c.2095G>C) in the general population?

ABCC6 p.Glu699Gln (c.2095G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC6 p.Glu699Gln (c.2095G>C)?

AlphaMissense predicts likely benign (score 0.1538) — an in-silico prediction, not a clinical call.

ABCC6 p.Glu699Gln

c.2095G>C · rs1445084199 · VCV2750303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1538 · 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	0.1538	likely benign
REVEL	0.476	indeterminate
SaProt	LLR -7.11	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 1.4	GERP -2.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic
Overall
CADD	22.3	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: ABCC6
Protein: p.Glu699Gln
Coding: c.2095G>C
MANE Select: NM_001171
dbSNP: rs1445084199
Type: single nucleotide variant
Location: chr16:16182564 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 699: a UniProt-annotated variant site (in pxe; does not change protein biosynthesis and folding); the abc transporter 1 domain

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

Similar variants

ABCC6 p.Glu699Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCC6 p.Glu699Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCC6 p.Glu699Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCC6 c.1868-5T>G Pathogenic/Likely pathogenic ★★ same type
ABCC6 c.2071-1G>A Likely pathogenic ★★ same type
ABCC6 c.2591-1G>T Likely pathogenic ★★ same type
ABCC6 c.2787+1G>T Pathogenic ★★ same type
ABCC6 c.3506+1G>A Pathogenic/Likely 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/abcc6-p-glu699gln (accessed [today's date]).

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