Is AMACR p.Pro16= (c.48G>A) pathogenic?

AMACR p.Pro16= (c.48G>A) is classified Conflicting classifications of pathogenicity in AMACR (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-12-04). Ultra-rare (popmax 0.0164%, mid); Associated with alpha-methylacyl-CoA racemase deficiency.

What condition is associated with AMACR p.Pro16= (c.48G>A)?

AMACR p.Pro16= (c.48G>A) is associated with alpha-methylacyl-CoA racemase deficiency (ClinVar).

How common is AMACR p.Pro16= (c.48G>A) in the general population?

AMACR p.Pro16= (c.48G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

AMACR p.Pro16=

c.48G>A · rs144271819 · VCV353256

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

alpha-methylacyl-CoA racemase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.6	GERP -3.1
Overall
CADD	9.139	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00124% 20/1,611,362 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Admixed American	0.00333%	29,990
Remaining individualsnot grpmax-eligible	0.0016%	62,420
European (non-Finnish)	0.00136%	73,727

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: AMACR
Protein: p.Pro16=
Coding: c.48G>A
MANE Select: NM_014324
dbSNP: rs144271819
Type: single nucleotide variant
Location: chr5:34007972 (GRCh38)
Gene constraint: LOEUF 1.239 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.79

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

Disease context

alpha-methylacyl-CoA racemase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AMACR p.Ser52Pro Pathogenic/Likely pathogenic ★★ same condition
AMACR c.*233T>C Uncertain significance ★★ same condition
AMACR p.Ala15Pro Uncertain significance ★★ ⚠ same condition
AMACR p.Ala189Glu Uncertain significance ★★ ⚠ same condition
AMACR p.Arg106Lys Uncertain significance ★★ ⚠ same condition
AMACR p.Arg171Cys Uncertain significance ★★ ⚠ same condition
AMACR p.Arg171His Uncertain significance ★★ ⚠ same condition
AMACR p.Arg173Cys Uncertain significance ★★ ⚠ same condition

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/amacr-p-pro16 (accessed [today's date]).

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