Is AFF2 p.Met784Arg (c.2351T>G) pathogenic?

AFF2 p.Met784Arg (c.2351T>G) is classified Likely benign in AFF2 (ClinVar, Single submitter, 3 submitters; last evaluated 2023-02-01). AlphaMissense: likely benign (0.1018); Ultra-rare (popmax 0.0416%, nfe).

How common is AFF2 p.Met784Arg (c.2351T>G) in the general population?

AFF2 p.Met784Arg (c.2351T>G) is ultra-rare (popmax 0.0416%, nfe) (gnomAD).

What do computational predictors say about AFF2 p.Met784Arg (c.2351T>G)?

AlphaMissense predicts likely benign (score 0.1018) — an in-silico prediction, not a clinical call.

AFF2 p.Met784Arg

c.2351T>G · rs147852345 · VCV2661609

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1018 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0416%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1018	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.091	GERP -2.2, phastCons 0.001
Regional constraint	o/e 0.94	unconstrained · MANE · 304 kb · p 0.17 · regional, not allelic
Overall
CADD	8.358	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0416% European (non-Finnish) · 372/895,033 alleles

Filtering AF 0.038% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0367%

Overall 0.0317% 383/1,209,697 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0416%	2,406
Remaining individualsnot grpmax-eligible	0.021%	4,762
Finnishnot grpmax-eligible	0.00215%	46,562

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: AFF2
Protein: p.Met784Arg
Coding: c.2351T>G
MANE Select: NM_002025
dbSNP: rs147852345
Type: single nucleotide variant
Location: chrX:148956396 (GRCh38)
Structure: AlphaFold pLDDT 49.27

Full AFF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AFF2 c.3267+5G>C Uncertain significance ★★ same type
AFF2 p.Ala1197Thr Uncertain significance ★★ ⚠ same type
AFF2 p.Ala171Pro Uncertain significance ★★ ⚠ same type
AFF2 p.Arg1238Cys Uncertain significance ★★ ⚠ same type
AFF2 p.Arg1295Cys Uncertain significance ★★ ⚠ same type
AFF2 p.Arg670His Uncertain significance ★★ ⚠ same type
AFF2 p.Asn77Ile Uncertain significance ★★ ⚠ same type
AFF2 p.Asp187Glu 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/aff2-p-met784arg (accessed [today's date]).

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