Is INTS1 p.Phe1264Leu (c.3792C>G) pathogenic?

INTS1 p.Phe1264Leu (c.3792C>G) is classified Uncertain significance in INTS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-01). AlphaMissense: likely pathogenic (0.8568); Absent from gnomAD v4.1.

How common is INTS1 p.Phe1264Leu (c.3792C>G) in the general population?

INTS1 p.Phe1264Leu (c.3792C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INTS1 p.Phe1264Leu (c.3792C>G)?

AlphaMissense predicts likely pathogenic (score 0.8568) — an in-silico prediction, not a clinical call.

INTS1 p.Phe1264Leu

c.3792C>G · VCV4084711

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8568 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8568	likely pathogenic
REVEL	0.035	moderately benign-leaning
SaProt	LLR -1.21	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.077, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 12 kb · p 0.001 · regional, not allelic
Overall
CADD	20.1	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

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: INTS1
Protein: p.Phe1264Leu
Coding: c.3792C>G
MANE Select: NM_001080453
Type: single nucleotide variant
Location: chr7:1481400 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.49 · 8 PDB
Residue 1264: an α-helix

Full INTS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

INTS1 c.3430-2A>C Likely pathogenic ★★ same type
INTS1 p.Arg101Ter Likely pathogenic ★★ same type
INTS1 p.Glu182Ter Likely pathogenic ★★ same type
INTS1 c.1283+5G>A Uncertain significance ★★ same type
INTS1 c.2977-5C>T Uncertain significance ★★ same type
INTS1 p.Ala1112Val Uncertain significance ★★ ⚠ same type
INTS1 p.Ala1505Val Uncertain significance ★★ ⚠ same type
INTS1 p.Ala1854Val 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/ints1-p-phe1264leu (accessed [today's date]).

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