Is DNAAF4 p.Lys299Arg (c.896A>G) pathogenic?

DNAAF4 p.Lys299Arg (c.896A>G) is classified Uncertain significance in DNAAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-10-05). AlphaMissense: likely benign (0.0882); Absent from gnomAD v4.1.

How common is DNAAF4 p.Lys299Arg (c.896A>G) in the general population?

DNAAF4 p.Lys299Arg (c.896A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAAF4 p.Lys299Arg (c.896A>G)?

AlphaMissense predicts likely benign (score 0.0882) — an in-silico prediction, not a clinical call.

DNAAF4 p.Lys299Arg

c.896A>G · rs1060503096 · VCV410965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0882 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0882	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.82	acceptor gain · deltas
Pangolin	Δ0.62	gain · loss 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 68 kb · p 7.4e-05 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: DNAAF4
Protein: p.Lys299Arg
Coding: c.896A>G
MANE Select: NM_130810
dbSNP: rs1060503096
Type: single nucleotide variant
Location: chr15:55435056 (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.Lys299= Likely benign ★ same residue
DNAAF4 c.1047+1G>A Pathogenic/Likely pathogenic ★★ same type
DNAAF4 c.1153+1G>A Pathogenic ★★ same type
DNAAF4 c.405+1G>A Likely pathogenic ★★ same type
DNAAF4 p.Arg245Ter Pathogenic/Likely pathogenic ★★ same type
DNAAF4 p.Arg270Ter Pathogenic/Likely pathogenic ★★ same type
DNAAF4 p.Arg330Trp Pathogenic/Likely pathogenic ★★ same type
DNAAF4 p.Arg371Ter Pathogenic/Likely pathogenic ★★ 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-lys299arg (accessed [today's date]).

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