Is AMER3 p.Pro137= (c.411C>T) pathogenic?

AMER3 p.Pro137= (c.411C>T) is classified Likely benign in AMER3 (ClinVar, No assertion criteria, 1 submitter). Ultra-rare (popmax 0.0134%, eas); Associated with EBV-positive nodal T- and NK-cell lymphoma.

What condition is associated with AMER3 p.Pro137= (c.411C>T)?

AMER3 p.Pro137= (c.411C>T) is associated with EBV-positive nodal T- and NK-cell lymphoma (ClinVar).

How common is AMER3 p.Pro137= (c.411C>T) in the general population?

AMER3 p.Pro137= (c.411C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

AMER3 p.Pro137=

c.411C>T · rs749518900 · VCV2681228

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

EBV-positive nodal T- and NK-cell lymphoma

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 -1.6	GERP -3.6
Overall
CADD	6.552	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,870 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000479% 7/1,460,848 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,478
European (non-Finnish)	8.47e-05%	1,180,002

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: AMER3
Protein: p.Pro137=
Coding: c.411C>T
MANE Select: NM_152698
dbSNP: rs749518900
Type: single nucleotide variant
Location: chr2:130762483 (GRCh38)
Structure: AlphaFold pLDDT 45.30

Full AMER3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EBV-positive nodal T- and NK-cell lymphoma

Similar variants

AMER3 p.Ala175Val Uncertain significance ★ ⚠ same type
AMER3 p.Ala25Thr Uncertain significance ★ ⚠ same type
AMER3 p.Ala345Ser Uncertain significance ★ ⚠ same type
AMER3 p.Ala402Asp Uncertain significance ★ ⚠ same type
AMER3 p.Ala557Thr Uncertain significance ★ ⚠ same type
AMER3 p.Ala55Thr Uncertain significance ★ ⚠ same type
AMER3 p.Ala579Thr Uncertain significance ★ ⚠ same type
AMER3 p.Ala588Pro Uncertain significance ★ ⚠ same type

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/amer3-p-pro137 (accessed [today's date]).

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