Is AMACR p.Pro325= (c.975C>T) pathogenic?

AMACR p.Pro325= (c.975C>T) is classified Likely benign in AMACR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-05). Ultra-rare (popmax 0.0147%, afr); Associated with alpha-methylacyl-CoA racemase deficiency.

What condition is associated with AMACR p.Pro325= (c.975C>T)?

AMACR p.Pro325= (c.975C>T) is associated with alpha-methylacyl-CoA racemase deficiency (ClinVar).

How common is AMACR p.Pro325= (c.975C>T) in the general population?

AMACR p.Pro325= (c.975C>T) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

AMACR p.Pro325=

c.975C>T · rs766116509 · VCV1582904

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

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 looked up on this page · why
Constraint at this position
Conservation	phyloP 0.74	GERP -4.3, phastCons 1
Overall
CADD	5.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,888 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000744% 12/1,613,956 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,808
European (non-Finnish)	8.47e-05%	1,179,993

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.Pro325=
Coding: c.975C>T
dbSNP: rs766116509
Type: single nucleotide variant
Location: chr5:33989267 (GRCh38)

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

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-pro325 (accessed [today's date]).

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