Is ABCD3 p.Arg117Cys (c.349C>T) pathogenic?

ABCD3 p.Arg117Cys (c.349C>T) is classified Uncertain significance in ABCD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-10-01). AlphaMissense: likely pathogenic (0.6917); Very rare (popmax 0.00223%, eas).

How common is ABCD3 p.Arg117Cys (c.349C>T) in the general population?

ABCD3 p.Arg117Cys (c.349C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ABCD3 p.Arg117Cys (c.349C>T)?

AlphaMissense predicts likely pathogenic (score 0.6917) — an in-silico prediction, not a clinical call.

ABCD3 p.Arg117Cys

c.349C>T · rs1474614063 · VCV806171

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6917 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6917	likely pathogenic
REVEL	0.871	moderately pathogenic-leaning
SaProt	LLR -11.50	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 23 kb · p 3.7e-09 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00223% East Asian · 1/44,790 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.00093% 15/1,612,212 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,790
Remaining individualsnot grpmax-eligible	0.0016%	62,430
South Asian	0.0011%	90,996
European (non-Finnish)	0.00102%	98,261

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.Arg117Cys
Coding: c.349C>T
MANE Select: NM_002858
dbSNP: rs1474614063
Type: single nucleotide variant
Location: chr1:94473779 (GRCh38)
Gene constraint: LOEUF 0.484 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 83.39 · 9 PDB
Residue 117: the abc transmembrane type-1 domain

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

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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-arg117cys (accessed [today's date]).

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