Is AFF2 p.Ser1037Ile (c.3110G>T) pathogenic?

AFF2 p.Ser1037Ile (c.3110G>T) is classified Likely benign in AFF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: ambiguous (0.3401); Ultra-rare (popmax 0.0175%, amr); Associated with Inborn genetic diseases.

What condition is associated with AFF2 p.Ser1037Ile (c.3110G>T)?

AFF2 p.Ser1037Ile (c.3110G>T) is associated with Inborn genetic diseases (ClinVar).

How common is AFF2 p.Ser1037Ile (c.3110G>T) in the general population?

AFF2 p.Ser1037Ile (c.3110G>T) is ultra-rare (popmax 0.0175%, amr) (gnomAD).

What do computational predictors say about AFF2 p.Ser1037Ile (c.3110G>T)?

AlphaMissense predicts ambiguous (score 0.3401) — an in-silico prediction, not a clinical call.

AFF2 p.Ser1037Ile

c.3110G>T · rs1557288854 · VCV3092444

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3401 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0175%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3401	ambiguous
REVEL	0.298	indeterminate
SaProt	LLR -7.96	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 304 kb · p 0.17 · regional, not allelic
Overall
CADD	25.1	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 0.0175% Admixed American · 8/45,737 alleles

Filtering AF 0.00869% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0063%

Overall 0.000661% 8/1,209,519 alleles · ultra-rare

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.Ser1037Ile
Coding: c.3110G>T
MANE Select: NM_002025
dbSNP: rs1557288854
Type: single nucleotide variant
Location: chrX:148966986 (GRCh38)
Structure: AlphaFold pLDDT 49.27

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-ser1037ile (accessed [today's date]).

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