Is ABCC6 p.Trp701Arg (c.2101T>C) pathogenic?

ABCC6 p.Trp701Arg (c.2101T>C) is classified Likely pathogenic in ABCC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely pathogenic (0.9283); Absent from gnomAD v4.1.

How common is ABCC6 p.Trp701Arg (c.2101T>C) in the general population?

ABCC6 p.Trp701Arg (c.2101T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC6 p.Trp701Arg (c.2101T>C)?

AlphaMissense predicts likely pathogenic (score 0.9283) — an in-silico prediction, not a clinical call.

ABCC6 p.Trp701Arg

c.2101T>C · rs2152258991 · VCV1396177

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9283 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9283	likely pathogenic ✓ concordant with ClinVar · top 1% in ABCC6
REVEL	0.837	moderately pathogenic-leaning
SaProt	LLR -11.81	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic
Overall
CADD	28.3	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

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.Trp701Arg
Coding: c.2101T>C
MANE Select: NM_001171
dbSNP: rs2152258991
Type: single nucleotide variant
Location: chr16:16182558 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 701: the abc transporter 1 domain

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

Similar variants

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
ABCC6 c.37-1G>A 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-trp701arg (accessed [today's date]).

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