Is DNALI1 p.Arg29Trp (c.85C>T) pathogenic?

DNALI1 p.Arg29Trp (c.85C>T) is classified Uncertain significance in DNALI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-16). AlphaMissense: likely benign (0.3004); Rare (popmax 0.116%, mid).

How common is DNALI1 p.Arg29Trp (c.85C>T) in the general population?

DNALI1 p.Arg29Trp (c.85C>T) is rare (popmax 0.116%, mid) (gnomAD).

What do computational predictors say about DNALI1 p.Arg29Trp (c.85C>T)?

AlphaMissense predicts likely benign (score 0.3004) — an in-silico prediction, not a clinical call.

DNALI1 p.Arg29Trp

c.85C>T · VCV3273143

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3004 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.116%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3004	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -9.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 8,063 bp · p 0.3 · regional, not allelic
Overall
CADD	23.9	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 0.116% Middle Eastern · 7/6,050 alleles

Filtering AF 0.0543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.00285% 46/1,612,602 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.116%	864
Remaining individualsnot grpmax-eligible	0.016%	6,244
African / African-American	0.00934%	10,706
East Asian	0.00446%	22,413
European (non-Finnish)	0.0017%	58,967

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: DNALI1
Protein: p.Arg29Trp
Coding: c.85C>T
MANE Select: NM_003462
Type: single nucleotide variant
Location: chr1:37557606 (GRCh38)
Gene constraint: LOEUF 1.202 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.32 · 1 PDB
Residue 29: the 'disordered' region

Full DNALI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNALI1 p.Arg29Gln Uncertain significance ★ ⚠ same residue
DNALI1 p.Leu196= Benign ★★ same type
DNALI1 p.Lys231Gln Benign ★★ ⚠ same type
DNALI1 p.Glu190Ter Likely pathogenic ★ same type
DNALI1 c.-21G>A Uncertain significance ★ same type
DNALI1 c.-29G>T Uncertain significance ★ same type
DNALI1 c.-42A>T Uncertain significance ★ same type
DNALI1 p.Ala144Val Uncertain significance ★ ⚠ 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/dnali1-p-arg29trp (accessed [today's date]).

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