Is DNALI1 p.Cys214Phe (c.641G>T) pathogenic?

DNALI1 p.Cys214Phe (c.641G>T) is classified Uncertain significance in DNALI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: ambiguous (0.4709); Absent from gnomAD v4.1.

How common is DNALI1 p.Cys214Phe (c.641G>T) in the general population?

DNALI1 p.Cys214Phe (c.641G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNALI1 p.Cys214Phe (c.641G>T)?

AlphaMissense predicts ambiguous (score 0.4709) — an in-silico prediction, not a clinical call.

DNALI1 p.Cys214Phe

c.641G>T · VCV4013711

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4709 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4709	ambiguous
REVEL	0.317	indeterminate
SaProt	LLR -11.22	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 8,063 bp · p 0.3 · regional, not allelic
Overall
CADD	24.5	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: DNALI1
Protein: p.Cys214Phe
Coding: c.641G>T
MANE Select: NM_003462
Type: single nucleotide variant
Location: chr1:37562145 (GRCh38)
Gene constraint: LOEUF 1.202 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.32 · 1 PDB
Residue 214: the 'disordered' region

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

Similar variants

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
DNALI1 p.Ala194Thr 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-cys214phe (accessed [today's date]).

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