Is ABCC6 p.Ser1205fs (c.3614_3615del) pathogenic?

ABCC6 p.Ser1205fs (c.36143615del) is classified Pathogenic in ABCC6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-13). Very rare (popmax 0.00153%, nfe); Associated with ABCC6-related disorder.

What condition is associated with ABCC6 p.Ser1205fs (c.3614_3615del)?

ABCC6 p.Ser1205fs (c.3614_3615del) is associated with ABCC6-related disorder (ClinVar).

How common is ABCC6 p.Ser1205fs (c.3614_3615del) in the general population?

ABCC6 p.Ser1205fs (c.3614_3615del) is very rare (popmax 0.00153%, nfe) (gnomAD).

ABCC6 p.Ser1205fs

c.3614_3615del · rs745900279 · VCV280870

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Conditions

ABCC6-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 25 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.67	GERP -0.45, phastCons 0.15
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00153% European (non-Finnish) · 18/1,180,040 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00273% 44/1,613,792 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0376%	2,658
Remaining individualsnot grpmax-eligible	0.0032%	31,237
European (non-Finnish)grpmax	0.00153%	65,558

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser1205fs
Coding: c.3614_3615del
MANE Select: NM_001171
dbSNP: rs745900279
Type: Microsatellite
Location: chr16:16161456 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 1205: the abc transmembrane type-1 2 domain

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

Disease context

ABCC6-related disorder

Similar variants

ABCC6 p.952FL[1] Likely pathogenic ★★ same condition
ABCC6 c.1868-5T>G Pathogenic/Likely pathogenic ★★ same condition
ABCC6 c.2071-1G>A Likely pathogenic ★★ same condition
ABCC6 c.3506+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC6 c.3506+2_3506+5del Pathogenic/Likely pathogenic ★★ same condition
ABCC6 c.3736-1G>A Pathogenic ★★ same condition
ABCC6 c.998+2_998+3del Pathogenic/Likely pathogenic ★★ same condition
ABCC6 p.Ala1303Pro 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-ser1205fs (accessed [today's date]).

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