Is DNAI4 p.Ser760Phe (c.2279C>T) pathogenic?

DNAI4 p.Ser760Phe (c.2279C>T) is classified Uncertain significance in DNAI4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.3265); Rare (popmax 0.119%, afr).

How common is DNAI4 p.Ser760Phe (c.2279C>T) in the general population?

DNAI4 p.Ser760Phe (c.2279C>T) is rare (popmax 0.119%, afr) (gnomAD).

What do computational predictors say about DNAI4 p.Ser760Phe (c.2279C>T)?

AlphaMissense predicts likely benign (score 0.3265) — an in-silico prediction, not a clinical call.

DNAI4 p.Ser760Phe

c.2279C>T · rs143078594 · VCV3084315

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3265 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.119%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3265	likely benign
REVEL	0.236	benign-leaning
SaProt	LLR -12.41	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 111 kb · p 0.79 · regional, not allelic
Overall
CADD	25.9	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

Grpmax group 0.119% African / African-American · 89/74,890 alleles

Filtering AF 0.0989% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0915%

Overall 0.00582% 94/1,613,958 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.119%	841
Admixed American	0.005%	20,001
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	8.47e-05%	1,180,016

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.Ser760Phe
Coding: c.2279C>T
MANE Select: NM_024763
dbSNP: rs143078594
Type: single nucleotide variant
Location: chr1:66826880 (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-ser760phe (accessed [today's date]).

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