Is DNAI1 p.Pro253Ser (c.757C>T) pathogenic?

DNAI1 p.Pro253Ser (c.757C>T) is classified Uncertain significance in DNAI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-31). AlphaMissense: likely benign (0.0849); Absent from gnomAD v4.1.

How common is DNAI1 p.Pro253Ser (c.757C>T) in the general population?

DNAI1 p.Pro253Ser (c.757C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAI1 p.Pro253Ser (c.757C>T)?

AlphaMissense predicts likely benign (score 0.0849) — an in-silico prediction, not a clinical call.

DNAI1 p.Pro253Ser

c.757C>T · VCV3603048

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0849 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0849	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -6.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.36, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 62 kb · p 0.35 · regional, not allelic
Overall
CADD	16.79	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

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: DNAI1
Protein: p.Pro253Ser
Coding: c.757C>T
MANE Select: NM_012144
Type: single nucleotide variant
Location: chr9:34493269 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.54 · 1 PDB

Full DNAI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAI1 p.Pro253Ala Uncertain significance ★★ ⚠ same residue
DNAI1 p.Pro253fs Likely pathogenic ★ same residue
DNAI1 c.1019+5G>C Pathogenic/Likely pathogenic ★★ same type
DNAI1 c.1063+1G>A Pathogenic/Likely pathogenic ★★ same type
DNAI1 c.1063+1G>T Pathogenic/Likely pathogenic ★★ same type
DNAI1 c.1402-1G>A Likely pathogenic ★★ same type
DNAI1 c.1490-2A>G Likely pathogenic ★★ same type
DNAI1 c.1569+1G>T Pathogenic/Likely pathogenic ★★ 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/dnai1-p-pro253ser (accessed [today's date]).

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