Is ABCB7 p.Pro496Leu (c.1487C>T) pathogenic?

ABCB7 p.Pro496Leu (c.1487C>T) is classified Uncertain significance in ABCB7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-06). AlphaMissense: likely benign (0.1389); Absent from gnomAD v4.1.

How common is ABCB7 p.Pro496Leu (c.1487C>T) in the general population?

ABCB7 p.Pro496Leu (c.1487C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCB7 p.Pro496Leu (c.1487C>T)?

AlphaMissense predicts likely benign (score 0.1389) — an in-silico prediction, not a clinical call.

ABCB7 p.Pro496Leu

c.1487C>T · rs1242447315 · VCV871573

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1389 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1389	likely benign
REVEL	0.752	pathogenic-leaning
SaProt	LLR -12.12	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 46 kb · p 3.2e-26 · regional, not allelic
Overall
CADD	24.1	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: ABCB7
Protein: p.Pro496Leu
Coding: c.1487C>T
MANE Select: NM_001271696
dbSNP: rs1242447315
Type: single nucleotide variant
Location: chrX:75069333 (GRCh38)
Structure: AlphaFold pLDDT 78.19 · 4 PDB
Residue 496: the abc transporter domain

Full ABCB7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB7 p.Pro496Ser Uncertain significance ★★ ⚠ same residue
ABCB7 c.1659+5T>G Uncertain significance ★★ same type
ABCB7 c.1935+5G>C Uncertain significance ★★ same type
ABCB7 p.Ala5Glu Uncertain significance ★★ ⚠ same type
ABCB7 p.Arg711His Uncertain significance ★★ ⚠ same type
ABCB7 p.Asn378Asp Uncertain significance ★★ ⚠ same type
ABCB7 p.Asp653Asn Uncertain significance ★★ ⚠ same type
ABCB7 p.Glu494Gln 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/abcb7-p-pro496leu (accessed [today's date]).

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