Is AMACR p.Lys50Arg (c.149A>G) pathogenic?

AMACR p.Lys50Arg (c.149A>G) is classified Uncertain significance in AMACR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-01). AlphaMissense: likely benign (0.2572); Very rare (popmax 0.00454%, eas); Associated with alpha-methylacyl-CoA racemase deficiency.

What condition is associated with AMACR p.Lys50Arg (c.149A>G)?

AMACR p.Lys50Arg (c.149A>G) is associated with alpha-methylacyl-CoA racemase deficiency (ClinVar).

How common is AMACR p.Lys50Arg (c.149A>G) in the general population?

AMACR p.Lys50Arg (c.149A>G) is very rare (popmax 0.00454%, eas) (gnomAD).

What do computational predictors say about AMACR p.Lys50Arg (c.149A>G)?

AlphaMissense predicts likely benign (score 0.2572) — an in-silico prediction, not a clinical call.

AMACR p.Lys50Arg

c.149A>G · rs1361002006 · VCV1710050

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2572 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00454%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

alpha-methylacyl-CoA racemase deficiency

Computational evidence

Protein change
AlphaMissense	0.2572	likely benign
REVEL	0.618	indeterminate
SaProt	LLR -7.34	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.54, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 19 kb · p 0.71 · regional, not allelic
Overall
CADD	25.0	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

Grpmax group 0.00454% East Asian · 2/44,094 alleles

Filtering AF 0.000752% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000281%

Overall 0.000208% 3/1,440,332 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00454%	22,047
Remaining individualsnot grpmax-eligible	0.00162%	61,734

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.Lys50Arg
Coding: c.149A>G
MANE Select: NM_014324
dbSNP: rs1361002006
Type: single nucleotide variant
Location: chr5:34007871 (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-lys50arg (accessed [today's date]).

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