Is A2M p.Thr813= (c.2439G>A) pathogenic?

A2M p.Thr813= (c.2439G>A) is classified Likely benign in A2M (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-27). Ultra-rare (popmax 0.0547%, afr); Associated with A2M-related disorder.

What condition is associated with A2M p.Thr813= (c.2439G>A)?

A2M p.Thr813= (c.2439G>A) is associated with A2M-related disorder (ClinVar).

How common is A2M p.Thr813= (c.2439G>A) in the general population?

A2M p.Thr813= (c.2439G>A) is ultra-rare (popmax 0.0547%, afr) (gnomAD).

A2M p.Thr813=

c.2439G>A · rs375292452 · VCV3041113

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0547%, afr)

Conditions

A2M-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.004	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.9	GERP -0.075
Overall
CADD	0.323	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0547% African / African-American · 41/75,008 alleles

Filtering AF 0.0413% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0367%

Overall 0.00273% 44/1,614,100 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0547%	1,829
Admixed American	0.00167%	60,022
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	8.47e-05%	1,180,008

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.Thr813=
Coding: c.2439G>A
MANE Select: NM_000014
dbSNP: rs375292452
Type: single nucleotide variant
Location: chr12:9091231 (GRCh38)
Gene constraint: LOEUF 0.765 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.61 · 13 PDB

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-thr813 (accessed [today's date]).

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