Is AFF2 p.Pro468= (c.1404C>T) pathogenic?

AFF2 p.Pro468= (c.1404C>T) is classified Likely benign in AFF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-04). Absent from gnomAD v4.1.

How common is AFF2 p.Pro468= (c.1404C>T) in the general population?

AFF2 p.Pro468= (c.1404C>T) is absent from gnomAD v4.1 (gnomAD).

AFF2 p.Pro468=

c.1404C>T · rs1603347355 · VCV723230

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.61	GERP -1.2
Overall
CADD	2.754	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AFF2
Protein: p.Pro468=
Coding: c.1404C>T
MANE Select: NM_002025
dbSNP: rs1603347355
Type: single nucleotide variant
Location: chrX:148953586 (GRCh38)
Structure: AlphaFold pLDDT 49.27
Residue 468: 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-pro468 (accessed [today's date]).

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