Is DNAI4 p.Ser613Pro (c.1837T>C) pathogenic?

DNAI4 p.Ser613Pro (c.1837T>C) is classified Uncertain significance in DNAI4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). AlphaMissense: likely pathogenic (0.9833); Very rare (popmax 0.00167%, amr).

How common is DNAI4 p.Ser613Pro (c.1837T>C) in the general population?

DNAI4 p.Ser613Pro (c.1837T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DNAI4 p.Ser613Pro (c.1837T>C)?

AlphaMissense predicts likely pathogenic (score 0.9833) — an in-silico prediction, not a clinical call.

DNAI4 p.Ser613Pro

c.1837T>C · VCV4242975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9833 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9833	likely pathogenic · top 2% in DNAI4
REVEL	0.519	indeterminate
SaProt	LLR -16.69	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 111 kb · p 0.79 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00167% Admixed American · 1/59,736 alleles

Overall 0.000124% 2/1,612,382 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,736
European (non-Finnish)	8.48e-05%	1,179,326

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: DNAI4
Protein: p.Ser613Pro
Coding: c.1837T>C
MANE Select: NM_024763
Type: single nucleotide variant
Location: chr1:66834045 (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-ser613pro (accessed [today's date]).

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