Is ABCD1 p.Ala646Ser (c.1936G>T) pathogenic?

ABCD1 p.Ala646Ser (c.1936G>T) is classified Uncertain significance in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.1501); Absent from gnomAD v4.1.

How common is ABCD1 p.Ala646Ser (c.1936G>T) in the general population?

ABCD1 p.Ala646Ser (c.1936G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCD1 p.Ala646Ser (c.1936G>T)?

AlphaMissense predicts likely benign (score 0.1501) — an in-silico prediction, not a clinical call.

ABCD1 p.Ala646Ser

c.1936G>T · VCV3899634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1501 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,202,071)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1501	likely benign
REVEL	0.687	pathogenic-leaning
SaProt	LLR -6.46	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 3,261 bp · p 4e-11 · regional, not allelic
Overall
CADD	21.9	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

No allele count reported in gnomAD v4.1 (AN 1,202,071). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCD1
Protein: p.Ala646Ser
Coding: c.1936G>T
MANE Select: NM_000033
Type: single nucleotide variant
Location: chrX:153743291 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 646: a UniProt-annotated variant site (in ald); an α-helix; the abc transporter domain

Full ABCD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCD1 p.Ala646Val Uncertain significance ★★ ⚠ same residue
ABCD1 p.Ala646= Likely benign ★★ same residue
ABCD1 c.1635-2A>G Pathogenic ★★ same type
ABCD1 c.1781-1G>C Pathogenic ★★ same type
ABCD1 c.1781-1G>T Pathogenic/Likely pathogenic ★★ same type
ABCD1 c.1866-10G>A Pathogenic/Likely pathogenic ★★ same type
ABCD1 c.1866-1G>C Likely pathogenic ★★ same type
ABCD1 c.1866-2A>T Likely pathogenic ★★ 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/abcd1-p-ala646ser (accessed [today's date]).

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