Is ABCB7 p.Pro496Ser (c.1486C>T) pathogenic?

ABCB7 p.Pro496Ser (c.1486C>T) is classified Uncertain significance in ABCB7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-01). AlphaMissense: likely benign (0.1647); Very rare (popmax 0.00654%, amr).

How common is ABCB7 p.Pro496Ser (c.1486C>T) in the general population?

ABCB7 p.Pro496Ser (c.1486C>T) is very rare (popmax 0.00654%, amr) (gnomAD).

What do computational predictors say about ABCB7 p.Pro496Ser (c.1486C>T)?

AlphaMissense predicts likely benign (score 0.1647) — an in-silico prediction, not a clinical call.

ABCB7 p.Pro496Ser

c.1486C>T · rs863223864 · VCV213977

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1647 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00654%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1647	likely benign
REVEL	0.625	indeterminate
SaProt	LLR -11.18	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 46 kb · p 3.2e-26 · regional, not allelic
Overall
CADD	23.8	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

Grpmax group 0.00654% Admixed American · 3/45,890 alleles

Filtering AF 0.00173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000881%

Overall 0.000273% 3/1,098,095 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: ABCB7
Protein: p.Pro496Ser
Coding: c.1486C>T
MANE Select: NM_001271696
dbSNP: rs863223864
Type: single nucleotide variant
Location: chrX:75069334 (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.Pro496Leu 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-pro496ser (accessed [today's date]).

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