Is ABCC6 p.Glu690Lys (c.2068G>A) pathogenic?

ABCC6 p.Glu690Lys (c.2068G>A) is classified Conflicting classifications of pathogenicity in ABCC6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-03-15). AlphaMissense: likely benign (0.0556); Very rare (popmax 0.00401%, afr).

How common is ABCC6 p.Glu690Lys (c.2068G>A) in the general population?

ABCC6 p.Glu690Lys (c.2068G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about ABCC6 p.Glu690Lys (c.2068G>A)?

AlphaMissense predicts likely benign (score 0.0556) — an in-silico prediction, not a clinical call.

ABCC6 p.Glu690Lys

c.2068G>A · rs773604010 · VCV2570933

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0556 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0556	likely benign
REVEL	0.349	indeterminate
SaProt	LLR -4.82	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.97	GERP -0.34, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic
Overall
CADD	12.3	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 0.00401% African / African-American · 3/74,856 alleles

Filtering AF 0.00247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00266% 43/1,613,766 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,952
European (non-Finnish)	0.00331%	30,255
South Asian	0.0011%	91,074

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.Glu690Lys
Coding: c.2068G>A
MANE Select: NM_001171
dbSNP: rs773604010
Type: single nucleotide variant
Location: chr16:16182806 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 690: the abc transporter 1 domain

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

Similar variants

ABCC6 p.Glu690Ter Pathogenic ★ 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
ABCC6 c.3507-1G>A Pathogenic ★★ same type
ABCC6 c.3507-2A>G 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-glu690lys (accessed [today's date]).

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