Is ABCB4 p.Val712= (c.2136C>T) pathogenic?

ABCB4 p.Val712= (c.2136C>T) is classified Conflicting classifications of pathogenicity in ABCB4 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-04-14). Ultra-rare (popmax 0.0329%, mid); Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB4 p.Val712= (c.2136C>T)?

ABCB4 p.Val712= (c.2136C>T) is associated with familial intrahepatic cholestasis (ClinVar).

How common is ABCB4 p.Val712= (c.2136C>T) in the general population?

ABCB4 p.Val712= (c.2136C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

ABCB4 p.Val712=

c.2136C>T · rs778345147 · VCV3023829

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

familial intrahepatic cholestasis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP 0.11, phastCons 0.99
Overall
CADD	9.085	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,082 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00285% 46/1,613,974 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,041
Admixed American	0.01%	10,000
African / African-American	0.00801%	12,485
Finnishnot grpmax-eligible	0.00781%	12,806
Remaining individualsnot grpmax-eligible	0.0064%	15,620
East Asian	0.00223%	44,874
South Asian	0.0022%	45,546
European (non-Finnish)	0.00169%	58,999

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: ABCB4
Protein: p.Val712=
Coding: c.2136C>T
MANE Select: NM_000443
dbSNP: rs778345147
Type: single nucleotide variant
Location: chr7:87423981 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 712: an α-helix; the abc transmembrane type-1 2 domain

Full ABCB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial intrahepatic cholestasis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCB4 p.Val712Ala Uncertain significance ⚠ same residue
ABCB4 c.2064+3A>T Likely pathogenic ★★ same condition
ABCB4 c.2682+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.2783+1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.286+1G>A Pathogenic ★★ same condition
ABCB4 c.3081+1G>C Pathogenic ★★ same condition
ABCB4 c.3486+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.3486+1G>T 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/abcb4-p-val712 (accessed [today's date]).

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