Is ABCB7 p.Ser638= (c.1914G>A) pathogenic?

ABCB7 p.Ser638= (c.1914G>A) is classified Likely benign in ABCB7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-31). Very rare (popmax 0.00874%, afr).

How common is ABCB7 p.Ser638= (c.1914G>A) in the general population?

ABCB7 p.Ser638= (c.1914G>A) is very rare (popmax 0.00874%, afr) (gnomAD).

ABCB7 p.Ser638=

c.1914G>A · VCV3606278

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00874%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -3.7
Overall
CADD	6.634	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00874% African / African-American · 5/57,214 alleles

Filtering AF 0.00338% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00215%

Overall 0.00257% 31/1,204,876 alleles · very rare exomes 28/1,092,890 · genomes 3/111,986 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00874%	11,443
Admixed American	0.00437%	22,867
Remaining individualsnot grpmax-eligible	0.00422%	23,713
European (non-Finnish)	0.00225%	44,527
Finnishnot grpmax-eligible	0.00215%	46,605
South Asian	0.00177%	56,653

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.Ser638=
Coding: c.1914G>A
MANE Select: NM_001271696
Type: single nucleotide variant
Location: chrX:75062349 (GRCh38)
Structure: AlphaFold pLDDT 78.19 · 4 PDB
Residue 638: the abc transporter domain

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-ser638 (accessed [today's date]).

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