Is AFF2 p.His164= (c.492T>C) pathogenic?

AFF2 p.His164= (c.492T>C) is classified Likely benign in AFF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-26). Very rare (popmax 0.00875%, amr); Associated with Inborn genetic diseases.

What condition is associated with AFF2 p.His164= (c.492T>C)?

AFF2 p.His164= (c.492T>C) is associated with Inborn genetic diseases (ClinVar).

How common is AFF2 p.His164= (c.492T>C) in the general population?

AFF2 p.His164= (c.492T>C) is very rare (popmax 0.00875%, amr) (gnomAD).

AFF2 p.His164=

c.492T>C · rs782760586 · VCV1744198

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00875%, amr)

Conditions

Inborn genetic diseases

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 -0.73	GERP -4.6, phastCons 0.004
Overall
CADD	1.512	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00875% Admixed American · 4/45,706 alleles

Filtering AF 0.00294% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00177%

Overall 0.000909% 11/1,209,554 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00875%	11,426
Remaining individualsnot grpmax-eligible	0.0042%	23,789
European (non-Finnish)	0.000559%	179,008

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: AFF2
Protein: p.His164=
Coding: c.492T>C
MANE Select: NM_002025
dbSNP: rs782760586
Type: single nucleotide variant
Location: chrX:148662219 (GRCh38)
Structure: AlphaFold pLDDT 49.27
Residue 164: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AFF2 p.Ala1197Thr Uncertain significance ★★ ⚠ same condition
AFF2 p.Arg1295Cys Uncertain significance ★★ ⚠ same condition
AFF2 p.Asp187Glu Uncertain significance ★★ ⚠ same condition
AFF2 p.Gln205Lys Uncertain significance ★★ ⚠ same condition
AFF2 p.Gly482Arg Uncertain significance ★★ ⚠ same condition
AFF2 p.Gly740Val Uncertain significance ★★ ⚠ same condition
AFF2 p.His1070Arg Uncertain significance ★★ ⚠ same condition
AFF2 p.His366Arg Uncertain significance ★★ ⚠ 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/aff2-p-his164 (accessed [today's date]).

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