Is DNAI3 p.Ser618Arg (c.1854T>G) pathogenic?

DNAI3 p.Ser618Arg (c.1854T>G) is classified Uncertain significance in DNAI3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely benign (0.2254); Ultra-rare (popmax 0.0987%, mid).

How common is DNAI3 p.Ser618Arg (c.1854T>G) in the general population?

DNAI3 p.Ser618Arg (c.1854T>G) is ultra-rare (popmax 0.0987%, mid) (gnomAD).

What do computational predictors say about DNAI3 p.Ser618Arg (c.1854T>G)?

AlphaMissense predicts likely benign (score 0.2254) — an in-silico prediction, not a clinical call.

DNAI3 p.Ser618Arg

c.1854T>G · rs764622021 · VCV2458514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2254 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0987%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2254	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -7.12	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 -6.4	GERP -3.5
Regional constraint	o/e 0.94	unconstrained · MANE · 28 kb · p 0.23 · regional, not allelic
Overall
CADD	0.009	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

Grpmax group 0.0987% Middle Eastern · 6/6,082 alleles

Filtering AF 0.0429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00868% 140/1,613,794 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0987%	1,014
South Asian	0.0439%	2,277
Remaining individualsnot grpmax-eligible	0.0144%	6,941
European (non-Finnish)	0.00687%	14,566
Admixed American	0.00667%	15,001

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: DNAI3
Protein: p.Ser618Arg
Coding: c.1854T>G
MANE Select: NM_145172
dbSNP: rs764622021
Type: single nucleotide variant
Location: chr1:85117796 (GRCh38)
Gene constraint: LOEUF 0.879 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.17 · 1 PDB

Full DNAI3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAI3 c.1350+6C>A Benign ★★ same type
DNAI3 p.Ala308Thr Benign ★★ same type
DNAI3 p.Arg79= Benign ★★ same type
DNAI3 p.Asp577= Benign ★★ same type
DNAI3 p.Glu458= Likely benign ★★ same type
DNAI3 p.Glu751= Benign ★★ same type
DNAI3 p.His788= Benign ★★ same type
DNAI3 p.His817= Benign ★★ 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/dnai3-p-ser618arg (accessed [today's date]).

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