Is AMACR p.Pro146= (c.438G>A) pathogenic?

AMACR p.Pro146= (c.438G>A) is classified Benign/Likely benign in AMACR (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-27). Low-frequency (popmax 1.28%, eas); Associated with alpha-methylacyl-CoA racemase deficiency.

What condition is associated with AMACR p.Pro146= (c.438G>A)?

AMACR p.Pro146= (c.438G>A) is associated with alpha-methylacyl-CoA racemase deficiency (ClinVar).

How common is AMACR p.Pro146= (c.438G>A) in the general population?

AMACR p.Pro146= (c.438G>A) is low-frequency (popmax 1.28%, eas) (gnomAD).

AMACR p.Pro146=

c.438G>A · rs140523570 · VCV507809

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.28%, eas)

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 -20	GERP -3.4
Overall
CADD	1.044	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.28% East Asian · 576/44,884 alleles

Filtering AF 1.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.16%

Overall 0.0392% 632/1,614,130 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.28%	78
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0128%	7,814
European (non-Finnish)	0.00347%	28,781
Admixed American	0.00333%	30,003
African / African-American	0.00267%	37,509
South Asian	0.0022%	45,540

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.Pro146=
Coding: c.438G>A
MANE Select: NM_014324
dbSNP: rs140523570
Type: single nucleotide variant
Location: chr5:34004688 (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.Pro146Leu Uncertain significance ★★ ⚠ same residue
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

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-pro146 (accessed [today's date]).

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