Is ABCB7 p.Ser641Leu (c.1922C>T) pathogenic?

ABCB7 p.Ser641Leu (c.1922C>T) is classified Uncertain significance in ABCB7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-16). AlphaMissense: ambiguous (0.5511); Ultra-rare (popmax 0.0123%, afr); Associated with Inborn genetic diseases.

What condition is associated with ABCB7 p.Ser641Leu (c.1922C>T)?

ABCB7 p.Ser641Leu (c.1922C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB7 p.Ser641Leu (c.1922C>T) in the general population?

ABCB7 p.Ser641Leu (c.1922C>T) is ultra-rare (popmax 0.0123%, afr) (gnomAD).

What do computational predictors say about ABCB7 p.Ser641Leu (c.1922C>T)?

AlphaMissense predicts ambiguous (score 0.5511) — an in-silico prediction, not a clinical call.

ABCB7 p.Ser641Leu

c.1922C>T · rs1002483499 · VCV2571371

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5511 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0123%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5511	ambiguous
REVEL	0.844	moderately pathogenic-leaning
SaProt	LLR -9.97	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.95, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 46 kb · p 3.2e-26 · regional, not allelic
Overall
CADD	25.9	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 0.0123% African / African-American · 7/57,047 alleles

Filtering AF 0.00568% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00406%

Overall 0.00191% 23/1,204,674 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0123%	8,150
Ashkenazi Jewishnot grpmax-eligible	0.00455%	21,967
Admixed American	0.00438%	22,840
Remaining individualsnot grpmax-eligible	0.00422%	23,710
South Asian	0.00353%	28,321
European (non-Finnish)	0.00101%	98,957

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.Ser641Leu
Coding: c.1922C>T
MANE Select: NM_001271696
dbSNP: rs1002483499
Type: single nucleotide variant
Location: chrX:75062341 (GRCh38)
Structure: AlphaFold pLDDT 78.19 · 4 PDB
Residue 641: the abc transporter domain; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCB7 p.Ala5Glu Uncertain significance ★★ ⚠ same condition
ABCB7 p.Asp653Asn Uncertain significance ★★ ⚠ same condition
ABCB7 p.Leu272Phe Uncertain significance ★★ ⚠ same condition
ABCB7 p.Leu395Val Uncertain significance ★★ ⚠ same condition
ABCB7 p.Met175Val Uncertain significance ★★ ⚠ same condition
ABCB7 p.Met441Val Uncertain significance ★★ ⚠ same condition
ABCB7 p.Thr187Ala Uncertain significance ★★ ⚠ same condition
ABCB7 p.Ala81Thr Benign/Likely benign ★★ same condition

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-ser641leu (accessed [today's date]).

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