Is DNAI4 p.Asn736Lys (c.2208T>G) pathogenic?

DNAI4 p.Asn736Lys (c.2208T>G) is classified Uncertain significance in DNAI4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: likely benign (0.1209); Ultra-rare (popmax 0.099%, mid).

How common is DNAI4 p.Asn736Lys (c.2208T>G) in the general population?

DNAI4 p.Asn736Lys (c.2208T>G) is ultra-rare (popmax 0.099%, mid) (gnomAD).

What do computational predictors say about DNAI4 p.Asn736Lys (c.2208T>G)?

AlphaMissense predicts likely benign (score 0.1209) — an in-silico prediction, not a clinical call.

DNAI4 p.Asn736Lys

c.2208T>G · VCV4242964

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1209 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.099%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1209	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -6.94	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 0.56	GERP -3.6
Regional constraint	o/e 1.01	unconstrained · MANE · 111 kb · p 0.79 · regional, not allelic
Overall
CADD	1.308	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 0.099% Middle Eastern · 6/6,062 alleles

Filtering AF 0.043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0294%

Overall 0.00285% 46/1,614,194 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.099%	1,010
South Asian	0.00769%	13,012
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	0.00254%	39,334
Admixed American	0.00167%	60,030

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.Asn736Lys
Coding: c.2208T>G
MANE Select: NM_024763
Type: single nucleotide variant
Location: chr1:66826951 (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-asn736lys (accessed [today's date]).

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