Is ABCB5 p.Phe709Ile (c.2125T>A) pathogenic?

ABCB5 p.Phe709Ile (c.2125T>A) is classified Uncertain significance in ABCB5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: ambiguous (0.5319); Absent from gnomAD v4.1.

How common is ABCB5 p.Phe709Ile (c.2125T>A) in the general population?

ABCB5 p.Phe709Ile (c.2125T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCB5 p.Phe709Ile (c.2125T>A)?

AlphaMissense predicts ambiguous (score 0.5319) — an in-silico prediction, not a clinical call.

ABCB5 p.Phe709Ile

c.2125T>A · rs2535061342 · VCV3122285

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5319 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5319	ambiguous
REVEL	0.791	moderately pathogenic-leaning
SaProt	LLR -8.74	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 132 kb · p 2.2e-15 · regional, not allelic
Overall
CADD	23.1	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.Phe709Ile
Coding: c.2125T>A
MANE Select: NM_001163941
dbSNP: rs2535061342
Type: single nucleotide variant
Location: chr7:20698521 (GRCh38)
Gene constraint: LOEUF 1.178 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.01
Residue 709: the abc transmembrane type-1 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-phe709ile (accessed [today's date]).

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