Is ABCD1 p.Asn214Ser (c.641A>G) pathogenic?

ABCD1 p.Asn214Ser (c.641A>G) is classified Uncertain significance in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.1076); Absent from gnomAD v4.1.

How common is ABCD1 p.Asn214Ser (c.641A>G) in the general population?

ABCD1 p.Asn214Ser (c.641A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCD1 p.Asn214Ser (c.641A>G)?

AlphaMissense predicts likely benign (score 0.1076) — an in-silico prediction, not a clinical call.

ABCD1 p.Asn214Ser

c.641A>G · VCV3776570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1076 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1076	likely benign
REVEL	0.537	indeterminate
SaProt	LLR -8.44	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 865 bp · p 0.3 · regional, not allelic
Overall
CADD	21.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCD1
Protein: p.Asn214Ser
Coding: c.641A>G
MANE Select: NM_000033
Type: single nucleotide variant
Location: chrX:153725907 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 214: an α-helix; a UniProt-annotated variant site (in ald); the abc transmembrane type-1 domain

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

Similar variants

ABCD1 p.Asn214Tyr Conflicting classifications of pathogenicity ★ ⚠ 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
ABCD1 c.901-1G>A 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-asn214ser (accessed [today's date]).

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