Is AFF4 p.Pro1044Arg (c.3131C>G) pathogenic?

AFF4 p.Pro1044Arg (c.3131C>G) is classified Uncertain significance in AFF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-31). AlphaMissense: likely pathogenic (0.6838); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AFF4 p.Pro1044Arg (c.3131C>G)?

AFF4 p.Pro1044Arg (c.3131C>G) is associated with Inborn genetic diseases (ClinVar).

How common is AFF4 p.Pro1044Arg (c.3131C>G) in the general population?

AFF4 p.Pro1044Arg (c.3131C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AFF4 p.Pro1044Arg (c.3131C>G)?

AlphaMissense predicts likely pathogenic (score 0.6838) — an in-silico prediction, not a clinical call.

AFF4 p.Pro1044Arg

c.3131C>G · VCV3840245

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6838 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6838	likely pathogenic
REVEL	0.797	moderately pathogenic-leaning
SaProt	LLR -8.84	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 5.7, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 8,017 bp · p 1.3e-12 · regional, not allelic
Overall
CADD	26.7	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: AFF4
Protein: p.Pro1044Arg
Coding: c.3131C>G
MANE Select: NM_014423
Type: single nucleotide variant
Location: chr5:132885088 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.62 · 9 PDB
Residue 1044: the 'disordered' region

Full AFF4 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

AFF4 p.Ala27Thr Uncertain significance ★★ ⚠ same condition
AFF4 p.Ala489Thr Uncertain significance ★★ ⚠ same condition
AFF4 p.Arg153His Uncertain significance ★★ ⚠ same condition
AFF4 p.Arg225His Uncertain significance ★★ ⚠ same condition
AFF4 p.Arg3Cys Uncertain significance ★★ ⚠ same condition
AFF4 p.Arg531Gln Uncertain significance ★★ ⚠ same condition
AFF4 p.Arg711Thr Uncertain significance ★★ ⚠ same condition
AFF4 p.Asn762Ser 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/aff4-p-pro1044arg (accessed [today's date]).

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