Is LARP1 p.Pro1069His (c.3206C>A) pathogenic?

LARP1 p.Pro1069His (c.3206C>A) is classified Uncertain significance in LARP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-07). Very rare (popmax 0.00223%, eas).

How common is LARP1 p.Pro1069His (c.3206C>A) in the general population?

LARP1 p.Pro1069His (c.3206C>A) is very rare (popmax 0.00223%, eas) (gnomAD).

LARP1 p.Pro1069His

c.3206C>A · rs2480746089 · VCV2482197

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.044	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.7, phastCons 0.34
Regional constraint	o/e 0.80	unconstrained · MANE · 2,779 bp · p 0.012 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,858 alleles

Overall 0.000124% 2/1,614,080 alleles · very rare exomes 2/1,461,884 · genomes 0/152,196 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,858
European (non-Finnish)	8.47e-05%	1,180,008

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.Pro1069His
Coding: c.3206C>A
MANE Select: NM_033551
dbSNP: rs2480746089
Type: single nucleotide variant
Location: chr5:154814011 (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.Pro1069Ser 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-pro1069his (accessed [today's date]).

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