Is HARS1 p.Arg484= (c.1452G>A) pathogenic?

HARS1 p.Arg484= (c.1452G>A) is classified Likely benign in HARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-26). Ultra-rare (popmax 0.0174%, afr); Associated with Usher syndrome type 3B.

What condition is associated with HARS1 p.Arg484= (c.1452G>A)?

HARS1 p.Arg484= (c.1452G>A) is associated with Usher syndrome type 3B (ClinVar).

How common is HARS1 p.Arg484= (c.1452G>A) in the general population?

HARS1 p.Arg484= (c.1452G>A) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

HARS1 p.Arg484=

c.1452G>A · rs149283940 · VCV1680284

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

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 -0.031	GERP -1.5, phastCons 0.81
Overall
CADD	5.912	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% African / African-American · 13/74,926 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.000991% 16/1,614,110 alleles · ultra-rare exomes 8/1,461,876 · genomes 8/152,234 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,764
Remaining individualsnot grpmax-eligible	0.0032%	31,243
Admixed American	0.00167%	60,012

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: HARS1
Protein: p.Arg484=
Coding: c.1452G>A
MANE Select: NM_002109
dbSNP: rs149283940
Type: single nucleotide variant
Location: chr5:140674685 (GRCh38)
Gene constraint: LOEUF 0.957 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.06 · 10 PDB

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 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
HARS1 p.Ala399Ser 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-arg484 (accessed [today's date]).

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