Is DNAAF4 p.Leu283Phe (c.849A>T) pathogenic?

DNAAF4 p.Leu283Phe (c.849A>T) is classified Uncertain significance in DNAAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-26). AlphaMissense: likely benign (0.2154); Very rare (popmax 0.00666%, afr); Associated with Inborn genetic diseases.

What condition is associated with DNAAF4 p.Leu283Phe (c.849A>T)?

DNAAF4 p.Leu283Phe (c.849A>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAAF4 p.Leu283Phe (c.849A>T) in the general population?

DNAAF4 p.Leu283Phe (c.849A>T) is very rare (popmax 0.00666%, afr) (gnomAD).

What do computational predictors say about DNAAF4 p.Leu283Phe (c.849A>T)?

AlphaMissense predicts likely benign (score 0.2154) — an in-silico prediction, not a clinical call.

DNAAF4 p.Leu283Phe

c.849A>T · VCV4241796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2154 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2154	likely benign
REVEL	0.448	indeterminate
SaProt	LLR -9.16	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP 0.35, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 68 kb · p 7.4e-05 · regional, not allelic
Overall
CADD	22.5	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

Grpmax group 0.00666% African / African-American · 5/75,054 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000372% 6/1,614,142 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00666%	15,011
Admixed American	0.00167%	60,010

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.Leu283Phe
Coding: c.849A>T
MANE Select: NM_130810
Type: single nucleotide variant
Location: chr15:55439516 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
DNAAF4 p.Glu286Asp 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-leu283phe (accessed [today's date]).

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