Is INTU p.Pro479= (c.1437A>G) pathogenic?

INTU p.Pro479= (c.1437A>G) is classified Likely benign in INTU (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-18). Absent from gnomAD v4.1.

How common is INTU p.Pro479= (c.1437A>G) in the general population?

INTU p.Pro479= (c.1437A>G) is absent from gnomAD v4.1 (gnomAD).

INTU p.Pro479=

c.1437A>G · VCV4724316

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.2	GERP -4.2
Overall
CADD	5.861	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: INTU
Protein: p.Pro479=
Coding: c.1437A>G
MANE Select: NM_015693
Type: single nucleotide variant
Location: chr4:127687855 (GRCh38)
Gene constraint: LOEUF 1.012 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.35 · 4 PDB
Residue 479: a UniProt-annotated variant site (in srtd7/20; in an srtd7/20 patient who also carries variant wdr35 l-311); a UniProt-annotated variant site (in srtd20; loss of subcellular location to cilium basal body, when tested in a heterologous system)

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

Similar variants

INTU p.Ala611Thr Uncertain significance ★★ ⚠ same type
INTU p.Ala804Val Uncertain significance ★★ ⚠ same type
INTU p.Arg119Thr Uncertain significance ★★ ⚠ same type
INTU p.Arg127Cys Uncertain significance ★★ ⚠ same type
INTU p.Arg510Gln Uncertain significance ★★ ⚠ same type
INTU p.Arg510Trp Uncertain significance ★★ ⚠ same type
INTU p.Arg665Cys Uncertain significance ★★ ⚠ same type
INTU p.Arg705Cys 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/intu-p-pro479 (accessed [today's date]).

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