Is LARP1 p.Pro1069Ser (c.3205C>T) pathogenic?

LARP1 p.Pro1069Ser (c.3205C>T) is classified Uncertain significance in LARP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). Very rare (popmax 8.47e-05%, nfe).

How common is LARP1 p.Pro1069Ser (c.3205C>T) in the general population?

LARP1 p.Pro1069Ser (c.3205C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

LARP1 p.Pro1069Ser

c.3205C>T · VCV4096608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.037	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.88	GERP -0.33, phastCons 0.12
Regional constraint	o/e 0.80	unconstrained · MANE · 2,779 bp · p 0.012 · regional, not allelic
Overall
CADD	16.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,000 alleles

Overall 6.2e-05% 1/1,614,070 alleles · very rare exomes 1/1,461,888 · genomes 0/152,182 · joint denominator

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: LARP1
Protein: p.Pro1069Ser
Coding: c.3205C>T
MANE Select: NM_033551
Type: single nucleotide variant
Location: chr5:154814010 (GRCh38)
Gene constraint: LOEUF 0.405 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.16 · 23 PDB
Residue 1069: the 'disordered' region; the 'required for interaction with rptor and for repression of mrnas with a 5'top motif' region

Full LARP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LARP1 p.Pro1069His Uncertain significance ★ same residue
LARP1 c.3081+5G>C Uncertain significance ★ same type
LARP1 p.Ala300Pro Uncertain significance ★ same type
LARP1 p.Ala524Glu Uncertain significance ★ same type
LARP1 p.Ala524Ser Uncertain significance ★ same type
LARP1 p.Ala524Val Uncertain significance ★ same type
LARP1 p.Ala764Thr Uncertain significance ★ same type
LARP1 p.Ala943Gly 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/larp1-p-pro1069ser (accessed [today's date]).

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