Is ABCD3 p.Val193Ala (c.578T>C) pathogenic?

ABCD3 p.Val193Ala (c.578T>C) is classified Uncertain significance in ABCD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-08). AlphaMissense: ambiguous (0.4814); Rare (popmax 0.116%, mid).

How common is ABCD3 p.Val193Ala (c.578T>C) in the general population?

ABCD3 p.Val193Ala (c.578T>C) is rare (popmax 0.116%, mid) (gnomAD).

What do computational predictors say about ABCD3 p.Val193Ala (c.578T>C)?

AlphaMissense predicts ambiguous (score 0.4814) — an in-silico prediction, not a clinical call.

ABCD3 p.Val193Ala

c.578T>C · VCV3604961

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4814 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.116%, mid)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4814	ambiguous
REVEL	0.93	moderately pathogenic-leaning
SaProt	LLR -11.61	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 23 kb · p 3.7e-09 · regional, not allelic
Overall
CADD	28.1	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 0.116% Middle Eastern · 7/6,026 alleles

Filtering AF 0.0544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0387%

Overall 0.0018% 29/1,610,636 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.116%	861
Admixed American	0.01%	9,988
Remaining individualsnot grpmax-eligible	0.0016%	62,384
European (non-Finnish)	0.00127%	78,476

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: ABCD3
Protein: p.Val193Ala
Coding: c.578T>C
MANE Select: NM_002858
Type: single nucleotide variant
Location: chr1:94475688 (GRCh38)
Gene constraint: LOEUF 0.484 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 83.39 · 9 PDB
Residue 193: an α-helix; the abc transmembrane type-1 domain

Full ABCD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCD3 p.Ala131Thr Uncertain significance ★★ ⚠ same type
ABCD3 p.Ala3Val Uncertain significance ★★ ⚠ same type
ABCD3 p.Arg496Cys Uncertain significance ★★ ⚠ same type
ABCD3 p.Asn12Tyr Uncertain significance ★★ ⚠ same type
ABCD3 p.Ile225Val Uncertain significance ★★ ⚠ same type
ABCD3 p.Leu23Val Uncertain significance ★★ ⚠ same type
ABCD3 p.Leu45Val Uncertain significance ★★ ⚠ same type
ABCD3 p.Pro425Leu 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/abcd3-p-val193ala (accessed [today's date]).

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