Is DNAI4 p.Pro43Ser (c.127C>T) pathogenic?

DNAI4 p.Pro43Ser (c.127C>T) is classified Uncertain significance in DNAI4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.1401); Very rare (popmax 0.00666%, amr).

How common is DNAI4 p.Pro43Ser (c.127C>T) in the general population?

DNAI4 p.Pro43Ser (c.127C>T) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about DNAI4 p.Pro43Ser (c.127C>T)?

AlphaMissense predicts likely benign (score 0.1401) — an in-silico prediction, not a clinical call.

DNAI4 p.Pro43Ser

c.127C>T · rs748648195 · VCV3084294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1401 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1401	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -5.63	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 2.2	GERP 0.84, phastCons 0.99
Regional constraint	o/e 1.01	unconstrained · MANE · 111 kb · p 0.79 · regional, not allelic
Overall
CADD	7.404	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 0.00666% Admixed American · 4/60,030 alleles

Filtering AF 0.00225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000274% 4/1,461,888 alleles · very rare

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.Pro43Ser
Coding: c.127C>T
MANE Select: NM_024763
dbSNP: rs748648195
Type: single nucleotide variant
Location: chr1:66924705 (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-pro43ser (accessed [today's date]).

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