Is A2M p.Lys502= (c.1506G>A) pathogenic?

A2M p.Lys502= (c.1506G>A) is classified Likely benign in A2M (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-28). Ultra-rare (popmax 0.0154%, amr); Associated with A2M-related disorder.

What condition is associated with A2M p.Lys502= (c.1506G>A)?

A2M p.Lys502= (c.1506G>A) is associated with A2M-related disorder (ClinVar).

How common is A2M p.Lys502= (c.1506G>A) in the general population?

A2M p.Lys502= (c.1506G>A) is ultra-rare (popmax 0.0154%, amr) (gnomAD).

A2M p.Lys502=

c.1506G>A · rs750247006 · VCV3038794

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, amr)

Conditions

A2M-related disorder

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 0.006	GERP 1.3, phastCons 0.24
Overall
CADD	5.923	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0154% Admixed American · 8/52,088 alleles

Filtering AF 0.00811% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00762%

Overall 0.00789% 123/1,559,498 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0154%	6,511
European (non-Finnish)	0.00964%	10,370
Remaining individualsnot grpmax-eligible	0.00661%	15,118

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: A2M
Protein: p.Lys502=
Coding: c.1506G>A
MANE Select: NM_000014
dbSNP: rs750247006
Type: single nucleotide variant
Location: chr12:9101196 (GRCh38)
Gene constraint: LOEUF 0.765 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.61 · 13 PDB
Residue 502: a disulfide bond

Full A2M gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

A2M-related disorder

Similar variants

A2M p.Ala981Ser Uncertain significance ★ ⚠ same condition
A2M c.1495-10T>C Likely benign same condition
A2M c.2597-4T>A Benign same condition
A2M p.Ala844Val Benign same condition
A2M p.Arg586Gln Likely benign same condition
A2M p.Arg704His Benign same condition
A2M p.Asn938Asp Likely benign ⚠ same condition
A2M p.Cys972Tyr Benign 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/a2m-p-lys502 (accessed [today's date]).

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