Is DNALI1 p.Ser7Pro (c.19T>C) pathogenic?

DNALI1 p.Ser7Pro (c.19T>C) is classified Uncertain significance in DNALI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: likely pathogenic (0.9579); Very rare (popmax 0.000339%, nfe).

How common is DNALI1 p.Ser7Pro (c.19T>C) in the general population?

DNALI1 p.Ser7Pro (c.19T>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about DNALI1 p.Ser7Pro (c.19T>C)?

AlphaMissense predicts likely pathogenic (score 0.9579) — an in-silico prediction, not a clinical call.

DNALI1 p.Ser7Pro

c.19T>C · VCV3841607

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9579 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9579	likely pathogenic
REVEL	0.354	indeterminate
SaProt	LLR -6.66	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 8,063 bp · p 0.3 · regional, not allelic
Overall
CADD	26.9	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

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,044 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,054 alleles · very rare exomes 3/1,461,894 · genomes 1/152,160 · joint denominator

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.Ser7Pro
Coding: c.19T>C
MANE Select: NM_003462
Type: single nucleotide variant
Location: chr1:37557013 (GRCh38)
Gene constraint: LOEUF 1.202 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.32 · 1 PDB
Residue 7: 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-ser7pro (accessed [today's date]).

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