Is ABCB8 p.Val202Ala (c.605T>C) pathogenic?

ABCB8 p.Val202Ala (c.605T>C) is classified Uncertain significance in ABCB8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). AlphaMissense: likely benign (0.1982); Very rare (popmax 8.47e-05%, nfe).

How common is ABCB8 p.Val202Ala (c.605T>C) in the general population?

ABCB8 p.Val202Ala (c.605T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ABCB8 p.Val202Ala (c.605T>C)?

AlphaMissense predicts likely benign (score 0.1982) — an in-silico prediction, not a clinical call.

ABCB8 p.Val202Ala

c.605T>C · rs1249215292 · VCV2321595

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1982 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1982	likely benign
REVEL	0.407	indeterminate
SaProt	LLR -6.56	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.4, phastCons 0.99
Regional constraint	o/e 0.93	unconstrained · MANE · 17 kb · p 0.036 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V219A vs ClinVar V202A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,014 alleles

Overall 6.84e-05% 1/1,461,312 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: ABCB8
Protein: p.Val202Ala
Coding: c.605T>C
MANE Select: NM_007188
dbSNP: rs1249215292
Type: single nucleotide variant
Location: chr7:151034545 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.01 · 2 PDB
Residue 202: an α-helix; the abc transmembrane type-1 domain

Full ABCB8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB8 p.Val202Ile Likely benign ★ ⚠ same residue
ABCB8 c.564+4C>T Benign ★★ same type
ABCB8 p.Ala101= Benign ★★ same type
ABCB8 p.Arg452Leu Benign ★★ ⚠ same type
ABCB8 p.His201= Benign ★★ same type
ABCB8 p.Leu124Val Benign ★★ same type
ABCB8 p.Ser39Asn Benign ★★ ⚠ same type
ABCB8 p.Val110= Benign ★★ 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/abcb8-p-val202ala (accessed [today's date]).

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