Is ABCC6 p.Val1107Ala (c.3320T>C) pathogenic?

ABCC6 p.Val1107Ala (c.3320T>C) is classified Conflicting classifications of pathogenicity in ABCC6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-09-18). AlphaMissense: likely benign (0.0558); Ultra-rare (popmax 0.0176%, sas); Associated with Inborn genetic diseases.

What condition is associated with ABCC6 p.Val1107Ala (c.3320T>C)?

ABCC6 p.Val1107Ala (c.3320T>C) is associated with Inborn genetic diseases, pseudoxanthoma elasticum, forme fruste, autosomal recessive inherited pseudoxanthoma elasticum (ClinVar).

How common is ABCC6 p.Val1107Ala (c.3320T>C) in the general population?

ABCC6 p.Val1107Ala (c.3320T>C) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

What do computational predictors say about ABCC6 p.Val1107Ala (c.3320T>C)?

AlphaMissense predicts likely benign (score 0.0558) — an in-silico prediction, not a clinical call.

ABCC6 p.Val1107Ala

c.3320T>C · rs780276741 · VCV1432078

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0558 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0558	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -3.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 0.75, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic
Overall
CADD	18.4	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 0.0176% South Asian · 16/91,088 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00888%

Overall 0.00248% 40/1,613,336 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,693
Middle Eastern	0.0164%	6,084
Admixed American	0.01%	9,998
Remaining individualsnot grpmax-eligible	0.0064%	15,619
African / African-American	0.004%	24,975
East Asian	0.00223%	44,884
European (non-Finnish)	0.000763%	131,113

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.Val1107Ala
Coding: c.3320T>C
MANE Select: NM_001171
dbSNP: rs780276741
Type: single nucleotide variant
Location: chr16:16163179 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 1107: the abc transmembrane type-1 2 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

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
ABCC6 c.3883-6G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC6 c.4209-2A>C Pathogenic/Likely 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-val1107ala (accessed [today's date]).

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