Is ARSG p.Pro255= (c.765T>C) pathogenic?

ARSG p.Pro255= (c.765T>C) is classified Benign in ARSG (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 63.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Usher syndrome, type 4.

What condition is associated with ARSG p.Pro255= (c.765T>C)?

ARSG p.Pro255= (c.765T>C) is associated with Usher syndrome, type 4 (ClinVar).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ARSG p.Pro255=

Q: How common is ARSG p.Pro255= (c.765T>C) in the general population?

ARSG p.Pro255= (c.765T>C) is common (popmax 63.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.765T>C · rs1558877 · VCV1165514

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 63.8%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Usher syndrome, type 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.98	GERP -3.5
Overall
CADD	1.559	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 63.8% African / African-American · 47,807/74,952 alleles

Filtering AF 63.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 63.1%

Overall 52.2% 841,665/1,613,214 alleles · common exomes 757,728/1,461,036 · genomes 83,937/152,178 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	63.8%	2
Amishnot grpmax-eligible	63.2%	2
Admixed American	63.2%	2
European (non-Finnish)	52.1%	2
Remaining individualsnot grpmax-eligible	51.2%	2
Finnishnot grpmax-eligible	50.3%	2
South Asian	50.3%	2
Ashkenazi Jewishnot grpmax-eligible	50.1%	2
Middle Eastern	49.9%	2
East Asian	28.5%	4

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: ARSG
Protein: p.Pro255=
Coding: c.765T>C
MANE Select: NM_001267727
dbSNP: rs1558877
Type: single nucleotide variant
Location: chr17:68368608 (GRCh38)
Gene constraint: LOEUF 0.996 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.90

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

Disease context

Usher syndrome, type 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

ARSG c.1092-5C>T Benign/Likely benign ★★ same condition
ARSG p.Thr236Ser Benign ★★ same condition
ARSG p.Trp274Arg Benign ★★ same condition
ARSG c.407-2A>C Likely pathogenic ★ same condition
ARSG c.982+1G>C Likely pathogenic ★ same condition
ARSG p.Trp274Ter Likely pathogenic ★ same condition
ARSG p.Arg342Trp Uncertain significance ★ ⚠ same condition
ARSG p.Arg424Cys 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/arsg-p-pro255 (accessed [today's date]).

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