Is ABCB7 p.Pro575Ser (c.1723C>T) pathogenic?

ABCB7 p.Pro575Ser (c.1723C>T) is classified Benign in ABCB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). AlphaMissense: likely benign (0.0954); Ultra-rare (popmax 0.0445%, eas).

How common is ABCB7 p.Pro575Ser (c.1723C>T) in the general population?

ABCB7 p.Pro575Ser (c.1723C>T) is ultra-rare (popmax 0.0445%, eas) (gnomAD).

What do computational predictors say about ABCB7 p.Pro575Ser (c.1723C>T)?

AlphaMissense predicts likely benign (score 0.0954) — an in-silico prediction, not a clinical call.

ABCB7 p.Pro575Ser

c.1723C>T · rs184486227 · VCV2189025

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0954 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0445%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0954	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -9.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP -1.5, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 46 kb · p 3.2e-26 · regional, not allelic
Overall
CADD	10.68	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 0.0445% East Asian · 15/33,723 alleles

Filtering AF 0.0274% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0221%

Overall 0.00166% 20/1,207,423 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0445%	2,248
Remaining individualsnot grpmax-eligible	0.00631%	15,844
South Asian	0.00176%	56,721
African / African-American	0.00175%	57,020

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.Pro575Ser
Coding: c.1723C>T
MANE Select: NM_001271696
dbSNP: rs184486227
Type: single nucleotide variant
Location: chrX:75065178 (GRCh38)
Structure: AlphaFold pLDDT 78.19 · 4 PDB
Residue 575: the abc transporter domain; an α-helix

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

Similar variants

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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
ABCB7 p.Gly197Cys 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-pro575ser (accessed [today's date]).

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