Is DNAL1 p.Ala2= (c.6G>A) pathogenic?

DNAL1 p.Ala2= (c.6G>A) is classified Likely benign in DNAL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-09). Ultra-rare (popmax 0.0391%, afr); Associated with primary ciliary dyskinesia 16.

What condition is associated with DNAL1 p.Ala2= (c.6G>A)?

DNAL1 p.Ala2= (c.6G>A) is associated with primary ciliary dyskinesia 16 (ClinVar).

How common is DNAL1 p.Ala2= (c.6G>A) in the general population?

DNAL1 p.Ala2= (c.6G>A) is ultra-rare (popmax 0.0391%, afr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DNAL1 p.Ala2=

c.6G>A · rs1265630707 · VCV695251

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0391%, afr)

Conditions

primary ciliary dyskinesia 16

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.063	GERP -3.5, phastCons 0.013
Overall
CADD	7.781	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0391% African / African-American · 27/69,122 alleles

Filtering AF 0.0276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0237%

Overall 0.00902% 136/1,507,530 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0391%	2,560
Middle Eastern	0.0178%	5,622
European (non-Finnish)	0.00865%	11,564
Admixed American	0.00707%	14,145
Remaining individualsnot grpmax-eligible	0.00687%	14,558
East Asian	0.00498%	20,062
South Asian	0.00131%	76,152

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: DNAL1
Protein: p.Ala2=
Coding: c.6G>A
MANE Select: NM_031427
dbSNP: rs1265630707
Type: single nucleotide variant
Location: chr14:73654849 (GRCh38)
Gene constraint: LOEUF 1.47 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.81 · 1 PDB
Residue 2: a modified residue (n-acetylalanine)

Full DNAL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 16 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DNAL1 p.Asn150Ser Pathogenic ★★ ⚠ same condition
DNAL1 p.Asn67Ser Uncertain significance ★★ ⚠ same condition
DNAL1 p.Glu164Lys Uncertain significance ★★ ⚠ same condition
DNAL1 p.Glu27Asp Uncertain significance ★★ ⚠ same condition
DNAL1 p.Ile34Val Uncertain significance ★★ ⚠ same condition
DNAL1 p.Ser157Ala Uncertain significance ★★ ⚠ same condition
DNAL1 p.Val148Ile Uncertain significance ★★ ⚠ same condition
DNAL1 c.153-12G>C Benign/Likely benign ★★ 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/dnal1-p-ala2 (accessed [today's date]).

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