Is A2M p.His893= (c.2679C>T) pathogenic?

A2M p.His893= (c.2679C>T) is classified Likely benign in A2M (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-14). Very rare (popmax 0.00314%, nfe); Associated with A2M-related disorder.

What condition is associated with A2M p.His893= (c.2679C>T)?

A2M p.His893= (c.2679C>T) is associated with A2M-related disorder (ClinVar).

How common is A2M p.His893= (c.2679C>T) in the general population?

A2M p.His893= (c.2679C>T) is very rare (popmax 0.00314%, nfe) (gnomAD).

A2M p.His893=

c.2679C>T · rs368199883 · VCV3052428

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Conditions

A2M-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.011	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.23	GERP -1.9
Overall
CADD	1.147	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00314% European (non-Finnish) · 37/1,178,378 alleles

Filtering AF 0.00232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00261% 42/1,611,216 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00314%	31,848
African / African-American	0.00268%	37,326
East Asian	0.00223%	44,830
Remaining individualsnot grpmax-eligible	0.0016%	62,344
South Asian	0.0011%	90,736

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.His893=
Coding: c.2679C>T
MANE Select: NM_000014
dbSNP: rs368199883
Type: single nucleotide variant
Location: chr12:9089941 (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-his893 (accessed [today's date]).

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