Is AFF4 p.Asp391= (c.1173C>T) pathogenic?

AFF4 p.Asp391= (c.1173C>T) is classified Likely benign in AFF4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-08). Very rare (popmax 0.000254%, nfe); Associated with AFF4-related disorder.

What condition is associated with AFF4 p.Asp391= (c.1173C>T)?

AFF4 p.Asp391= (c.1173C>T) is associated with AFF4-related disorder (ClinVar).

How common is AFF4 p.Asp391= (c.1173C>T) in the general population?

AFF4 p.Asp391= (c.1173C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

AFF4 p.Asp391=

c.1173C>T · VCV3347213

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

AFF4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.369	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 6, phastCons 1
Overall
CADD	11.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,178,954 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000496% 8/1,612,066 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00627%	15,938
Remaining individualsnot grpmax-eligible	0.0016%	62,366
European (non-Finnish)grpmax	0.000254%	392,984

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: AFF4
Protein: p.Asp391=
Coding: c.1173C>T
MANE Select: NM_014423
Type: single nucleotide variant
Location: chr5:132899602 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.62 · 9 PDB
Residue 391: the 'disordered' region

Full AFF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AFF4-related disorder

Similar variants

AFF4 p.Asp391Asn Uncertain significance ★ ⚠ same residue
AFF4 p.Glu657Asp Uncertain significance ★★ ⚠ same condition
AFF4 p.Ser839Cys Uncertain significance ★★ ⚠ same condition
AFF4 p.Ala551Thr Uncertain significance ★ ⚠ same condition
AFF4 p.Arg209Ser Uncertain significance ★ ⚠ same condition
AFF4 p.Arg725Lys Uncertain significance ★ ⚠ same condition
AFF4 p.Asp422Gly Uncertain significance ★ ⚠ same condition
AFF4 p.Pro611Leu 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-asp391 (accessed [today's date]).

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