Is ABCB11 p.Ala614Val (c.1841C>T) pathogenic?

ABCB11 p.Ala614Val (c.1841C>T) is classified Uncertain significance in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-30). AlphaMissense: ambiguous (0.3854); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with ABCB11 p.Ala614Val (c.1841C>T)?

ABCB11 p.Ala614Val (c.1841C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB11 p.Ala614Val (c.1841C>T) in the general population?

ABCB11 p.Ala614Val (c.1841C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ABCB11 p.Ala614Val (c.1841C>T)?

AlphaMissense predicts ambiguous (score 0.3854) — an in-silico prediction, not a clinical call.

ABCB11 p.Ala614Val

c.1841C>T · VCV3290408

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3854 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3854	ambiguous
REVEL	0.787	moderately pathogenic-leaning
SaProt	LLR -11.74	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 12	GERP 2.1, phastCons 1
Overall
CADD	25.2	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 0.00267% African / African-American · 2/74,924 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000205% 3/1,460,348 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,462
European (non-Finnish)	8.48e-05%	1,179,116

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: ABCB11
Protein: p.Ala614Val
Coding: c.1841C>T
MANE Select: NM_003742
Type: single nucleotide variant
Location: chr2:168969520 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.23 · 9 PDB
Residue 614: the abc transporter 1 domain

Full ABCB11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCB11 p.Ala614= Likely benign ★ same residue
ABCB11 p.Ala1283Thr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Ala693Thr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Asp1236Tyr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Cys1117Tyr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Glu395Asp Uncertain significance ★★ ⚠ same condition
ABCB11 p.Leu581Val Uncertain significance ★★ ⚠ same condition
ABCB11 p.Leu644Pro Uncertain significance ★★ ⚠ 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/abcb11-p-ala614val (accessed [today's date]).

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