Is AFF2 p.Phe48Tyr (c.143T>A) pathogenic?

AFF2 p.Phe48Tyr (c.143T>A) is classified Uncertain significance in AFF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-16). AlphaMissense: ambiguous (0.3953); Absent from gnomAD v4.1.

How common is AFF2 p.Phe48Tyr (c.143T>A) in the general population?

AFF2 p.Phe48Tyr (c.143T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AFF2 p.Phe48Tyr (c.143T>A)?

AlphaMissense predicts ambiguous (score 0.3953) — an in-silico prediction, not a clinical call.

AFF2 p.Phe48Tyr

c.143T>A · VCV3731196

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3953 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3953	ambiguous
REVEL	0.263	benign-leaning
SaProt	LLR -7.81	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.28, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 161 kb · p 0.93 · regional, not allelic
Overall
CADD	25.2	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

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.Phe48Tyr
Coding: c.143T>A
MANE Select: NM_002025
Type: single nucleotide variant
Location: chrX:148652094 (GRCh38)
Structure: AlphaFold pLDDT 49.27

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

Similar variants

AFF2 p.Phe48Leu Uncertain significance ★ ⚠ same residue
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

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-phe48tyr (accessed [today's date]).

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