Is AMACR p.Glu319= (c.957G>A) pathogenic?

AMACR p.Glu319= (c.957G>A) is classified Likely benign in AMACR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-31). Very rare (popmax 0.00891%, eas); Associated with alpha-methylacyl-CoA racemase deficiency.

What condition is associated with AMACR p.Glu319= (c.957G>A)?

AMACR p.Glu319= (c.957G>A) is associated with alpha-methylacyl-CoA racemase deficiency (ClinVar).

How common is AMACR p.Glu319= (c.957G>A) in the general population?

AMACR p.Glu319= (c.957G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

AMACR p.Glu319=

c.957G>A · VCV4701723

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00891%, 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 -0.67	GERP -0.75
Overall
CADD	0.642	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,886 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000274% 4/1,461,858 alleles · very rare

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.Glu319=
Coding: c.957G>A
MANE Select: NM_014324
Type: single nucleotide variant
Location: chr5:33989285 (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-glu319 (accessed [today's date]).

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