Is AFF2 p.Val704= (c.2112G>A) pathogenic?

AFF2 p.Val704= (c.2112G>A) is classified Likely benign in AFF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-06). Very rare (popmax 0.00177%, sas).

How common is AFF2 p.Val704= (c.2112G>A) in the general population?

AFF2 p.Val704= (c.2112G>A) is very rare (popmax 0.00177%, sas) (gnomAD).

AFF2 p.Val704=

c.2112G>A · rs1603348363 · VCV756909

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00177%, sas)

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 0.32	GERP -0.15, phastCons 0.97
Overall
CADD	3.498	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00177% South Asian · 1/56,524 alleles

Overall 0.000166% 2/1,208,321 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00177%	56,524
African / African-American	0.00177%	56,625

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.Val704=
Coding: c.2112G>A
MANE Select: NM_002025
dbSNP: rs1603348363
Type: single nucleotide variant
Location: chrX:148956157 (GRCh38)
Structure: AlphaFold pLDDT 49.27
Residue 704: the 'disordered' region

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-val704 (accessed [today's date]).

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