Is ABCB10 p.Phe513Ser (c.1538T>C) pathogenic?

ABCB10 p.Phe513Ser (c.1538T>C) is classified Uncertain significance in ABCB10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely pathogenic (0.852); Very rare (popmax 8.47e-05%, nfe).

How common is ABCB10 p.Phe513Ser (c.1538T>C) in the general population?

ABCB10 p.Phe513Ser (c.1538T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ABCB10 p.Phe513Ser (c.1538T>C)?

AlphaMissense predicts likely pathogenic (score 0.852) — an in-silico prediction, not a clinical call.

ABCB10 p.Phe513Ser

c.1538T>C · VCV4636052

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.852 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.852	likely pathogenic
REVEL	0.901	moderately pathogenic-leaning
SaProt	LLR -14.76	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 40 kb · p 1.5e-09 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,030 alleles

Overall 6.84e-05% 1/1,461,892 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: ABCB10
Protein: p.Phe513Ser
Coding: c.1538T>C
MANE Select: NM_012089
Type: single nucleotide variant
Location: chr1:229530306 (GRCh38)
Gene constraint: LOEUF 1.142 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.37 · 6 PDB
Residue 513: the abc transporter domain; a β-strand

Full ABCB10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB10 p.Asn478Lys Benign ★★ same type
ABCB10 p.Thr179= Benign ★★ same type
ABCB10 p.Ala110Pro Uncertain significance ★ ⚠ same type
ABCB10 p.Ala280Val Uncertain significance ★ ⚠ same type
ABCB10 p.Ala300Pro Uncertain significance ★ ⚠ same type
ABCB10 p.Ala388Gly Uncertain significance ★ ⚠ same type
ABCB10 p.Ala394Thr Uncertain significance ★ ⚠ same type
ABCB10 p.Ala461Val Uncertain significance ★ ⚠ 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/abcb10-p-phe513ser (accessed [today's date]).

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