Is STRC p.Arg344Ter (c.1030C>T) pathogenic?

STRC p.Arg344Ter (c.1030C>T) is classified Pathogenic in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). Very rare (popmax 0.00453%, sas); Associated with nonsyndromic genetic hearing loss.

What condition is associated with STRC p.Arg344Ter (c.1030C>T)?

STRC p.Arg344Ter (c.1030C>T) is associated with nonsyndromic genetic hearing loss (ClinVar).

How common is STRC p.Arg344Ter (c.1030C>T) in the general population?

STRC p.Arg344Ter (c.1030C>T) is very rare (popmax 0.00453%, sas) (gnomAD).

How is Rare non-syndromic genetic deafness inherited?

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

STRC p.Arg344Ter

c.1030C>T · rs1189167614 · VCV2582670

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 0.00453%, sas)

Conditions

nonsyndromic genetic hearing loss

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 29
Splicing
SpliceAI	Δ0.20	donor gain · deltas
Pangolin	Δ0.32	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.8	GERP -0.34, phastCons 1
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 0.00453% South Asian · 2/44,188 alleles

Filtering AF 0.00225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00166%

Overall 0.00327% 13/398,022 alleles · very rare exomes 13/386,732 · genomes 0/11,290 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00453%	22,094
Remaining individualsnot grpmax-eligible	0.00439%	22,782
European (non-Finnish)	0.00425%	23,536

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.Arg344Ter
Coding: c.1030C>T
MANE Select: NM_153700
dbSNP: rs1189167614
Type: single nucleotide variant
Location: chr15:43616536 (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

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

For Rare non-syndromic genetic deafness (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

STRC p.Arg1073Ter Pathogenic ★★ same condition
STRC p.Arg1391Gly Conflicting classifications of pathogenicity ★ same condition
STRC c.4219-1G>A Pathogenic/Likely pathogenic ★★ same type
STRC c.4701+1G>A Pathogenic/Likely pathogenic ★★ same type
STRC p.Arg1154Ter Pathogenic/Likely pathogenic ★★ same type
STRC p.Arg1224Ter Pathogenic ★★ same type
STRC p.Arg1338Ter Pathogenic/Likely pathogenic ★★ same type
STRC p.Arg1451Ter Pathogenic/Likely pathogenic ★★ 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/strc-p-arg344ter (accessed [today's date]).

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