Is ABCG8 p.Thr401Ser (c.1201A>T) pathogenic?

ABCG8 p.Thr401Ser (c.1201A>T) is classified Conflicting classifications of pathogenicity in ABCG8 (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1125); Low-frequency (popmax 1.27%, mid); Associated with Cardiovascular phenotype.

What condition is associated with ABCG8 p.Thr401Ser (c.1201A>T)?

ABCG8 p.Thr401Ser (c.1201A>T) is associated with Cardiovascular phenotype, sitosterolemia, sitosterolemia 1 (ClinVar).

How common is ABCG8 p.Thr401Ser (c.1201A>T) in the general population?

ABCG8 p.Thr401Ser (c.1201A>T) is low-frequency (popmax 1.27%, mid) (gnomAD).

What do computational predictors say about ABCG8 p.Thr401Ser (c.1201A>T)?

AlphaMissense predicts likely benign (score 0.1125) — an in-silico prediction, not a clinical call.

ABCG8 p.Thr401Ser

c.1201A>T · rs144200355 · VCV198901

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.1125 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.27%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1125	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -7.82	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 1.6	GERP -0.92
Regional constraint	o/e 1.29	unconstrained · MANE · 39 kb · p 8.8e-18 · regional, not allelic
Overall
CADD	13.17	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 1.27% Middle Eastern · 77/6,062 alleles

Filtering AF 1.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.958%

Overall 0.207% 3,339/1,613,736 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.27%	79
Admixed American	0.308%	324
European (non-Finnish)	0.243%	412
Remaining individualsnot grpmax-eligible	0.186%	539
African / African-American	0.0533%	1,875
South Asian	0.045%	2,221
Finnishnot grpmax-eligible	0.0204%	4,906
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401

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.Thr401Ser
Coding: c.1201A>T
MANE Select: NM_022437
dbSNP: rs144200355
Type: single nucleotide variant
Location: chr2:43872296 (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 401: an α-helix

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: sitosterolemia sitosterolemia 1 gallbladder disease 4

Similar variants

ABCG8 p.Thr401Met Uncertain significance ★★ ⚠ same residue
ABCG8 p.Thr401= Conflicting classifications of pathogenicity ★ same residue
ABCG8 c.64-2A>G Pathogenic ★★ same condition
ABCG8 c.965-1G>C Pathogenic ★★ same condition
ABCG8 p.Arg121Ter Pathogenic ★★ same condition
ABCG8 p.Arg164Ter Pathogenic ★★ same condition
ABCG8 p.Arg405Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCG8 p.Arg412Ter 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/abcg8-p-thr401ser (accessed [today's date]).

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