Is ABCB7 p.Ser751Leu (c.2252C>T) pathogenic?

ABCB7 p.Ser751Leu (c.2252C>T) is classified Benign in ABCB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: ambiguous (0.363); Very rare (popmax 0.00704%, sas).

How common is ABCB7 p.Ser751Leu (c.2252C>T) in the general population?

ABCB7 p.Ser751Leu (c.2252C>T) is very rare (popmax 0.00704%, sas) (gnomAD).

What do computational predictors say about ABCB7 p.Ser751Leu (c.2252C>T)?

AlphaMissense predicts ambiguous (score 0.363) — an in-silico prediction, not a clinical call.

ABCB7 p.Ser751Leu

c.2252C>T · rs372891558 · VCV3610721

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.363 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00704%, sas)

Computational evidence

Protein change
AlphaMissense	0.363	ambiguous
REVEL	0.583	indeterminate
SaProt	LLR -7.88	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 46 kb · p 3.2e-26 · regional, not allelic
Overall
CADD	26.3	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 0.00704% South Asian · 4/56,821 alleles

Filtering AF 0.00234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00141%

Overall 0.00141% 17/1,209,845 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00704%	14,205
Admixed American	0.00218%	45,832
African / African-American	0.00175%	57,246
European (non-Finnish)	0.00123%	81,376

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.Ser751Leu
Coding: c.2252C>T
MANE Select: NM_001271696
dbSNP: rs372891558
Type: single nucleotide variant
Location: chrX:75053377 (GRCh38)
Structure: AlphaFold pLDDT 78.19 · 4 PDB

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

Similar variants

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
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-ser751leu (accessed [today's date]).

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