Is DNAAF4 p.Phe34Val (c.100T>G) pathogenic?

DNAAF4 p.Phe34Val (c.100T>G) is classified Uncertain significance in DNAAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely benign (0.2352); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DNAAF4 p.Phe34Val (c.100T>G)?

DNAAF4 p.Phe34Val (c.100T>G) is associated with Inborn genetic diseases (ClinVar).

How common is DNAAF4 p.Phe34Val (c.100T>G) in the general population?

DNAAF4 p.Phe34Val (c.100T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAAF4 p.Phe34Val (c.100T>G)?

AlphaMissense predicts likely benign (score 0.2352) — an in-silico prediction, not a clinical call.

DNAAF4 p.Phe34Val

c.100T>G · VCV4241795

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2352 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2352	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -10.50	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 68 kb · p 7.4e-05 · regional, not allelic
Overall
CADD	23.0	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.Phe34Val
Coding: c.100T>G
MANE Select: NM_130810
Type: single nucleotide variant
Location: chr15:55498230 (GRCh38)
Gene constraint: LOEUF 1.018 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.00
Residue 34: the cs domain; the 'mediates interaction with esr1 and stub1' region

Full DNAAF4 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

DNAAF4 p.Phe34= Likely benign ★★ same residue
DNAAF4 p.Ala391Val Uncertain significance ★★ ⚠ same condition
DNAAF4 p.Arg233His Uncertain significance ★★ ⚠ same condition
DNAAF4 p.Arg245Gln Uncertain significance ★★ ⚠ same condition
DNAAF4 p.Arg410Leu Uncertain significance ★★ ⚠ same condition
DNAAF4 p.Arg410Trp Uncertain significance ★★ ⚠ same condition
DNAAF4 p.Gln4Arg Uncertain significance ★★ ⚠ same condition
DNAAF4 p.Glu222Lys 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/dnaaf4-p-phe34val (accessed [today's date]).

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