Is DNAI4 p.Pro587Ser (c.1759C>T) pathogenic?

DNAI4 p.Pro587Ser (c.1759C>T) is classified Uncertain significance in DNAI4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: ambiguous (0.4529); Absent from gnomAD v4.1.

How common is DNAI4 p.Pro587Ser (c.1759C>T) in the general population?

DNAI4 p.Pro587Ser (c.1759C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAI4 p.Pro587Ser (c.1759C>T)?

AlphaMissense predicts ambiguous (score 0.4529) — an in-silico prediction, not a clinical call.

DNAI4 p.Pro587Ser

c.1759C>T · rs2549269186 · VCV3084303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4529 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4529	ambiguous
REVEL	0.81	moderately pathogenic-leaning
SaProt	LLR -12.01	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 111 kb · p 0.79 · regional, not allelic
Overall
CADD	25.4	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: DNAI4
Protein: p.Pro587Ser
Coding: c.1759C>T
MANE Select: NM_024763
dbSNP: rs2549269186
Type: single nucleotide variant
Location: chr1:66834123 (GRCh38)
Gene constraint: LOEUF 0.862 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.48 · 1 PDB

Full DNAI4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAI4 p.Ala222Pro Uncertain significance ★ ⚠ same type
DNAI4 p.Ala328Ser Uncertain significance ★ ⚠ same type
DNAI4 p.Ala381Thr Uncertain significance ★ ⚠ same type
DNAI4 p.Ala463Glu Uncertain significance ★ ⚠ same type
DNAI4 p.Ala562Val Uncertain significance ★ ⚠ same type
DNAI4 p.Ala661Thr Uncertain significance ★ ⚠ same type
DNAI4 p.Ala75Thr Uncertain significance ★ ⚠ same type
DNAI4 p.Ala789Val 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/dnai4-p-pro587ser (accessed [today's date]).

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