Is ABCC6 p.Ala916Val (c.2747C>T) pathogenic?

ABCC6 p.Ala916Val (c.2747C>T) is classified Uncertain significance in ABCC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-06). AlphaMissense: likely benign (0.0784); Absent from gnomAD v4.1.

How common is ABCC6 p.Ala916Val (c.2747C>T) in the general population?

ABCC6 p.Ala916Val (c.2747C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC6 p.Ala916Val (c.2747C>T)?

AlphaMissense predicts likely benign (score 0.0784) — an in-silico prediction, not a clinical call.

ABCC6 p.Ala916Val

c.2747C>T · rs2047172419 · VCV2072232

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0784 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0784	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.69	donor gain · deltas
Pangolin	Δ0.62	gain · loss 0.45 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.9	GERP 0.098, phastCons 0.96
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.Ala916Val
Coding: c.2747C>T
MANE Select: NM_001171
dbSNP: rs2047172419
Type: single nucleotide variant
Location: chr16:16173324 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 916: the 'disordered' region

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-ala916val (accessed [today's date]).

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