Is ABCB5 p.Ser1059Phe (c.3176C>T) pathogenic?

ABCB5 p.Ser1059Phe (c.3176C>T) is classified Uncertain significance in ABCB5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). AlphaMissense: ambiguous (0.4811); Absent from gnomAD v4.1.

How common is ABCB5 p.Ser1059Phe (c.3176C>T) in the general population?

ABCB5 p.Ser1059Phe (c.3176C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCB5 p.Ser1059Phe (c.3176C>T)?

AlphaMissense predicts ambiguous (score 0.4811) — an in-silico prediction, not a clinical call.

ABCB5 p.Ser1059Phe

c.3176C>T · rs1782610966 · VCV2556913

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4811 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4811	ambiguous
REVEL	0.504	indeterminate
SaProt	LLR -8.81	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 0.11, phastCons 0.28
Regional constraint	o/e 1.20	unconstrained · MANE · 132 kb · p 2.2e-15 · regional, not allelic
Overall
CADD	20.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCB5
Protein: p.Ser1059Phe
Coding: c.3176C>T
MANE Select: NM_001163941
dbSNP: rs1782610966
Type: single nucleotide variant
Location: chr7:20743028 (GRCh38)
Gene constraint: LOEUF 1.178 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.01
Residue 1059: the abc transporter 2 domain

Full ABCB5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB5 p.Ala350Thr Likely benign ★★ same type
ABCB5 p.Val1209Ala Likely benign ★★ same type
ABCB5 p.Ala1112Thr Uncertain significance ★ ⚠ same type
ABCB5 p.Ala1154Gly Uncertain significance ★ ⚠ same type
ABCB5 p.Ala221Val Uncertain significance ★ ⚠ same type
ABCB5 p.Ala223Ser Uncertain significance ★ ⚠ same type
ABCB5 p.Ala327Thr Uncertain significance ★ ⚠ same type
ABCB5 p.Ala501Glu 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/abcb5-p-ser1059phe (accessed [today's date]).

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