Is ABCD3 p.Ala3Val (c.8C>T) pathogenic?

ABCD3 p.Ala3Val (c.8C>T) is classified Uncertain significance in ABCD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-13). AlphaMissense: likely benign (0.1658); Ultra-rare (popmax 0.0153%, nfe).

How common is ABCD3 p.Ala3Val (c.8C>T) in the general population?

ABCD3 p.Ala3Val (c.8C>T) is ultra-rare (popmax 0.0153%, nfe) (gnomAD).

What do computational predictors say about ABCD3 p.Ala3Val (c.8C>T)?

AlphaMissense predicts likely benign (score 0.1658) — an in-silico prediction, not a clinical call.

ABCD3 p.Ala3Val

c.8C>T · rs150616788 · VCV2981452

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1658 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0153%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1658	likely benign
REVEL	0.479	indeterminate
SaProt	LLR -6.90	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 46 kb · p 0.19 · regional, not allelic
Overall
CADD	23.1	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 0.0153% European (non-Finnish) · 180/1,177,852 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0127%

Overall 0.0119% 190/1,600,616 alleles · ultra-rare exomes 176/1,448,448 · genomes 14/152,168 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0153%	6,544
Remaining individualsnot grpmax-eligible	0.00967%	10,342
African / African-American	0.00535%	18,679

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.Ala3Val
Coding: c.8C>T
MANE Select: NM_002858
dbSNP: rs150616788
Type: single nucleotide variant
Location: chr1:94418486 (GRCh38)
Gene constraint: LOEUF 0.484 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 83.39 · 9 PDB
Residue 3: the 'interaction with pex19' region

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

Similar variants

ABCD3 p.Ala3= Likely benign ★ same residue
ABCD3 p.Ala131Thr 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-ala3val (accessed [today's date]).

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