Is DNAAF4 p.Val358Ala (c.1073T>C) pathogenic?

DNAAF4 p.Val358Ala (c.1073T>C) is classified Uncertain significance in DNAAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-20). AlphaMissense: ambiguous (0.5294); Absent from gnomAD v4.1.

How common is DNAAF4 p.Val358Ala (c.1073T>C) in the general population?

DNAAF4 p.Val358Ala (c.1073T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAAF4 p.Val358Ala (c.1073T>C)?

AlphaMissense predicts ambiguous (score 0.5294) — an in-silico prediction, not a clinical call.

DNAAF4 p.Val358Ala

c.1073T>C · rs1595889282 · VCV651131

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5294 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5294	ambiguous
REVEL	0.254	benign-leaning
SaProt	LLR -5.85	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.57	acceptor loss, 6 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 68 kb · p 7.4e-05 · regional, not allelic
Overall
CADD	25.5	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: DNAAF4
Protein: p.Val358Ala
Coding: c.1073T>C
MANE Select: NM_130810
dbSNP: rs1595889282
Type: single nucleotide variant
Location: chr15:55432577 (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 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
DNAAF4 p.Gln4Ter 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-val358ala (accessed [today's date]).

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