Is ABCB7 p.Ala5Val (c.14C>T) pathogenic?

ABCB7 p.Ala5Val (c.14C>T) is classified Uncertain significance in ABCB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-25). AlphaMissense: likely benign (0.2168); Ultra-rare (popmax 0.0534%, mid).

How common is ABCB7 p.Ala5Val (c.14C>T) in the general population?

ABCB7 p.Ala5Val (c.14C>T) is ultra-rare (popmax 0.0534%, mid) (gnomAD).

What do computational predictors say about ABCB7 p.Ala5Val (c.14C>T)?

AlphaMissense predicts likely benign (score 0.2168) — an in-silico prediction, not a clinical call.

ABCB7 p.Ala5Val

c.14C>T · VCV4951640

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2168 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0534%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2168	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -6.95	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 2	GERP 0.92, phastCons 0.75
Regional constraint	o/e 1.16	unconstrained · MANE · 57 kb · p 0.12 · regional, not allelic
Overall
CADD	6.227	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0534% Middle Eastern · 2/3,745 alleles

Filtering AF 0.00943% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00395%

Overall 0.000582% 7/1,202,976 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0534%	1,873
Admixed American	0.00442%	22,627
Remaining individualsnot grpmax-eligible	0.00212%	47,228
European (non-Finnish)	0.000224%	446,020

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.Ala5Val
Coding: c.14C>T
MANE Select: NM_001271696
Type: single nucleotide variant
Location: chrX:75156259 (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 p.Ala5Glu Uncertain significance ★★ ⚠ same residue
ABCB7 c.1659+5T>G Uncertain significance ★★ same type
ABCB7 c.1935+5G>C 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-ala5val (accessed [today's date]).

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