Is ABCG8 p.Ser129Ter (c.386C>A) pathogenic?

ABCG8 p.Ser129Ter (c.386C>A) is classified Pathogenic in ABCG8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). Very rare (popmax 0.00659%, sas).

How common is ABCG8 p.Ser129Ter (c.386C>A) in the general population?

ABCG8 p.Ser129Ter (c.386C>A) is very rare (popmax 0.00659%, sas) (gnomAD).

ABCG8 p.Ser129Ter

c.386C>A · rs762540907 · VCV2416955

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.4, phastCons 1
Overall
CADD	38.0	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 0.00659% South Asian · 6/91,074 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00041% 6/1,461,880 alleles · very rare

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: ABCG8
Protein: p.Ser129Ter
Coding: c.386C>A
MANE Select: NM_022437
dbSNP: rs762540907
Type: single nucleotide variant
Location: chr2:43851647 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.94 · 8 PDB
Residue 129: the abc transporter domain

Full ABCG8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCG8 p.Ser129Thr Uncertain significance ★★ ⚠ same residue
ABCG8 c.64-2A>G Pathogenic ★★ same type
ABCG8 c.964+1G>T Likely pathogenic ★★ same type
ABCG8 c.965-1G>C Pathogenic ★★ same type
ABCG8 p.Arg121Ter Pathogenic ★★ same type
ABCG8 p.Arg164Ter Pathogenic ★★ same type
ABCG8 p.Arg405Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
ABCG8 p.Arg412Ter Pathogenic/Likely 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/abcg8-p-ser129ter (accessed [today's date]).

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