Is ABCD2 p.Lys98Glu (c.292A>G) pathogenic?

ABCD2 p.Lys98Glu (c.292A>G) is classified Uncertain significance in ABCD2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-10-03). AlphaMissense: likely benign (0.1285); Ultra-rare (popmax 0.0108%, nfe).

How common is ABCD2 p.Lys98Glu (c.292A>G) in the general population?

ABCD2 p.Lys98Glu (c.292A>G) is ultra-rare (popmax 0.0108%, nfe) (gnomAD).

What do computational predictors say about ABCD2 p.Lys98Glu (c.292A>G)?

AlphaMissense predicts likely benign (score 0.1285) — an in-silico prediction, not a clinical call.

ABCD2 p.Lys98Glu

c.292A>G · rs373396030 · VCV559120

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1285 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1285	likely benign
REVEL	0.456	indeterminate
SaProt	LLR -10.31	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 3.4	GERP 2.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 646 bp · p 0.32 · regional, not allelic
Overall
CADD	18.82	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 0.0108% European (non-Finnish) · 128/1,180,036 alleles

Filtering AF 0.00928% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00871%

Overall 0.00929% 150/1,613,992 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0234%	4,269
Remaining individualsnot grpmax-eligible	0.0112%	8,926
European (non-Finnish)grpmax	0.0108%	9,219

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ABCD2
Protein: p.Lys98Glu
Coding: c.292A>G
MANE Select: NM_005164
dbSNP: rs373396030
Type: single nucleotide variant
Location: chr12:39619324 (GRCh38)
Gene constraint: LOEUF 0.714 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.65
Residue 98: the 'interaction with pex19' region

Full ABCD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCD2 c.1878-18G>C Benign/Likely benign ★★ same type
ABCD2 p.Ala251Gly Uncertain significance ★ ⚠ same type
ABCD2 p.Ala273Thr Uncertain significance ★ ⚠ same type
ABCD2 p.Ala489Glu Uncertain significance ★ ⚠ same type
ABCD2 p.Arg16Thr Uncertain significance ★ ⚠ same type
ABCD2 p.Arg178Cys Uncertain significance ★ ⚠ same type
ABCD2 p.Arg178His Uncertain significance ★ ⚠ same type
ABCD2 p.Arg337Cys 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/abcd2-p-lys98glu (accessed [today's date]).

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