Is ABCD1 p.Pro49His (c.146C>A) pathogenic?

ABCD1 p.Pro49His (c.146C>A) is classified Uncertain significance in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-04). AlphaMissense: likely benign (0.0994); Absent from gnomAD v4.1.

How common is ABCD1 p.Pro49His (c.146C>A) in the general population?

ABCD1 p.Pro49His (c.146C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCD1 p.Pro49His (c.146C>A)?

AlphaMissense predicts likely benign (score 0.0994) — an in-silico prediction, not a clinical call.

ABCD1 p.Pro49His

c.146C>A · rs1557052213 · VCV452488

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0994	likely benign
REVEL	0.292	indeterminate
SaProt	LLR -8.94	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 0.38, phastCons 0.006
Regional constraint	o/e 0.94	unconstrained · MANE · 865 bp · p 0.3 · regional, not allelic
Overall
CADD	14.88	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.Pro49His
Coding: c.146C>A
MANE Select: NM_000033
dbSNP: rs1557052213
Type: single nucleotide variant
Location: chrX:153725412 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB

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

Similar variants

ABCD1 p.Pro49Ser Uncertain significance ★ ⚠ same residue
ABCD1 p.Pro49= Likely benign ★ same residue
ABCD1 p.Pro49fs Pathogenic ★ 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

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-pro49his (accessed [today's date]).

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