Is STRC p.Arg849Ter (c.2545C>T) pathogenic?

STRC p.Arg849Ter (c.2545C>T) is classified Pathogenic in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). Very rare (popmax 0.00693%, sas); Associated with autosomal recessive nonsyndromic hearing loss 16.

What condition is associated with STRC p.Arg849Ter (c.2545C>T)?

STRC p.Arg849Ter (c.2545C>T) is associated with autosomal recessive nonsyndromic hearing loss 16 (ClinVar).

How common is STRC p.Arg849Ter (c.2545C>T) in the general population?

STRC p.Arg849Ter (c.2545C>T) is very rare (popmax 0.00693%, sas) (gnomAD).

STRC p.Arg849Ter

c.2545C>T · rs1437200449 · VCV2445651

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00693%, sas)

Conditions

autosomal recessive nonsyndromic hearing loss 16

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 29
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.42	GERP 0.4, phastCons 0.027
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00693% South Asian · 3/43,280 alleles

Filtering AF 0.00184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000909%

Overall 0.00173% 6/346,462 alleles · very rare exomes 5/313,964 · genomes 1/32,498 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00693%	14,427
Remaining individualsnot grpmax-eligible	0.00597%	16,762
European (non-Finnish)	0.000961%	104,096

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: STRC
Protein: p.Arg849Ter
Coding: c.2545C>T
MANE Select: NM_153700
dbSNP: rs1437200449
Type: single nucleotide variant
Location: chr15:43613167 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.21

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

Disease context

autosomal recessive nonsyndromic hearing loss 16 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STRC c.4219-1G>A Pathogenic/Likely pathogenic ★★ same condition
STRC c.4701+1G>A Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1073Ter Pathogenic ★★ same condition
STRC p.Arg1154Ter Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1224Ter Pathogenic ★★ same condition
STRC p.Arg1338Ter Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1451Ter Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1468Ter Pathogenic ★★ 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/strc-p-arg849ter (accessed [today's date]).

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