Is ABCC6 p.Ser1307Phe (c.3920C>T) pathogenic?

ABCC6 p.Ser1307Phe (c.3920C>T) is classified Uncertain significance in ABCC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-19). AlphaMissense: ambiguous (0.5425); Very rare (popmax 0.00187%, amr); Associated with pseudoxanthoma elasticum, forme fruste.

What condition is associated with ABCC6 p.Ser1307Phe (c.3920C>T)?

ABCC6 p.Ser1307Phe (c.3920C>T) is associated with pseudoxanthoma elasticum, forme fruste, autosomal recessive inherited pseudoxanthoma elasticum, arterial calcification, generalized, of infancy, 2 (ClinVar).

How common is ABCC6 p.Ser1307Phe (c.3920C>T) in the general population?

ABCC6 p.Ser1307Phe (c.3920C>T) is very rare (popmax 0.00187%, amr) (gnomAD).

What do computational predictors say about ABCC6 p.Ser1307Phe (c.3920C>T)?

AlphaMissense predicts ambiguous (score 0.5425) — an in-silico prediction, not a clinical call.

ABCC6 p.Ser1307Phe

c.3920C>T · VCV3578547

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5425 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00187%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

pseudoxanthoma elasticum, forme fruste

Computational evidence

Protein change
AlphaMissense	0.5425	ambiguous
REVEL	0.862	moderately pathogenic-leaning
SaProt	LLR -13.75	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic
Overall
CADD	31.0	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 0.00187% Admixed American · 1/53,354 alleles

Overall 0.000141% 2/1,416,490 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00187%	53,354
European (non-Finnish)	8.64e-05%	1,157,290

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.Ser1307Phe
Coding: c.3920C>T
MANE Select: NM_001171
Type: single nucleotide variant
Location: chr16:16154994 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 1307: an α-helix; the abc transporter 2 domain

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

Disease context

pseudoxanthoma elasticum, forme fruste — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

ABCC6 p.Ser1307Pro Likely pathogenic same residue
ABCC6 p.Ser1307= Likely benign ★ same residue
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

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-ser1307phe (accessed [today's date]).

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