Is HARS1 p.Pro261= (c.783T>G) pathogenic?

HARS1 p.Pro261= (c.783T>G) is classified Likely benign in HARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-10). Absent from gnomAD v4.1; Associated with Usher syndrome type 3B.

What condition is associated with HARS1 p.Pro261= (c.783T>G)?

HARS1 p.Pro261= (c.783T>G) is associated with Usher syndrome type 3B (ClinVar).

How common is HARS1 p.Pro261= (c.783T>G) in the general population?

HARS1 p.Pro261= (c.783T>G) is absent from gnomAD v4.1 (gnomAD).

HARS1 p.Pro261=

c.783T>G · rs1050248 · VCV2077956

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Usher syndrome type 3B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.8
Overall
CADD	0.005	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: HARS1
Protein: p.Pro261=
Coding: c.783T>G
MANE Select: NM_002109
dbSNP: rs1050248
Type: single nucleotide variant
Location: chr5:140677367 (GRCh38)
Gene constraint: LOEUF 0.957 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.06 · 10 PDB
Residue 261: an α-helix

Full HARS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Usher syndrome type 3B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HARS1 p.Pro261Arg Uncertain significance ★ ⚠ same residue
HARS1 c.1195-1G>A Uncertain significance ★★ same condition
HARS1 c.1311+4T>C Uncertain significance ★★ same condition
HARS1 c.1312-1G>A Uncertain significance ★★ same condition
HARS1 c.631-3C>A Uncertain significance ★★ same condition
HARS1 c.90+4A>C Uncertain significance ★★ same condition
HARS1 c.952-3C>A Uncertain significance ★★ same condition
HARS1 p.Ala2Thr Uncertain significance ★★ ⚠ same condition

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/hars1-p-pro261 (accessed [today's date]).

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