Is ABCD3 p.Asn12Tyr (c.34A>T) pathogenic?

ABCD3 p.Asn12Tyr (c.34A>T) is classified Uncertain significance in ABCD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-11). AlphaMissense: likely benign (0.1284); Ultra-rare (popmax 0.0469%, eas).

How common is ABCD3 p.Asn12Tyr (c.34A>T) in the general population?

ABCD3 p.Asn12Tyr (c.34A>T) is ultra-rare (popmax 0.0469%, eas) (gnomAD).

What do computational predictors say about ABCD3 p.Asn12Tyr (c.34A>T)?

AlphaMissense predicts likely benign (score 0.1284) — an in-silico prediction, not a clinical call.

ABCD3 p.Asn12Tyr

c.34A>T · rs767019118 · VCV2993533

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1284 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0469%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1284	likely benign
REVEL	0.6	indeterminate
SaProt	LLR -10.71	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 0.27, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 46 kb · p 0.19 · regional, not allelic
Overall
CADD	24.3	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 0.0469% East Asian · 21/44,772 alleles

Filtering AF 0.0314% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0263%

Overall 0.00137% 22/1,605,560 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0469%	2,132
Admixed American	0.00167%	59,868

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.Asn12Tyr
Coding: c.34A>T
MANE Select: NM_002858
dbSNP: rs767019118
Type: single nucleotide variant
Location: chr1:94418512 (GRCh38)
Gene constraint: LOEUF 0.484 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 83.39 · 9 PDB
Residue 12: the 'interaction with pex19' region

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

Similar variants

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ABCD3 p.Ala3Val Uncertain significance ★★ ⚠ same type
ABCD3 p.Arg496Cys 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
ABCD3 p.Pro425Ser 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-asn12tyr (accessed [today's date]).

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