Is DNAAF4 p.Gln166fs (c.496dup) pathogenic?

DNAAF4 p.Gln166fs (c.496dup) is classified Pathogenic in DNAAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-07). Very rare (popmax 0.00414%, afr).

How common is DNAAF4 p.Gln166fs (c.496dup) in the general population?

DNAAF4 p.Gln166fs (c.496dup) is very rare (popmax 0.00414%, afr) (gnomAD).

DNAAF4 p.Gln166fs

c.496dup · rs1450498773 · VCV2733790

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00414%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP -1.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00414% African / African-American · 3/72,536 alleles

Filtering AF 0.0011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000505%

Overall 0.000214% 3/1,400,392 alleles · very 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: DNAAF4
Protein: p.Gln166fs
Coding: c.496dup
MANE Select: NM_130810
dbSNP: rs1450498773
Type: Duplication
Location: chr15:55467070 (GRCh38)
Gene constraint: LOEUF 1.018 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.00

Full DNAAF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAAF4 p.Ile175Asnfs Pathogenic/Likely pathogenic ★★ same type
DNAAF4 p.Ile144fs Pathogenic ★ same type
DNAAF4 p.Ile195fs Conflicting classifications of pathogenicity ★ same type
DNAAF4 c.1047+135dup Likely benign ★ same type
DNAAF4 c.1047+17_1047+18dup Likely benign ★ same type
DNAAF4 c.1048-190dup Benign ★ same type
DNAAF4 c.-255-19_-255-10dup Likely benign ★ same type
DNAAF4 c.-255-28_-255-10dup Likely benign ★ 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/dnaaf4-p-gln166fs (accessed [today's date]).

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