Is STRC p.Arg1073Ter (c.3217C>T) pathogenic?

STRC p.Arg1073Ter (c.3217C>T) is classified Pathogenic in STRC (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-21). Very rare (popmax 0.00465%, sas); Associated with Monogenic hearing loss.

What condition is associated with STRC p.Arg1073Ter (c.3217C>T)?

STRC p.Arg1073Ter (c.3217C>T) is associated with Monogenic hearing loss, autosomal recessive nonsyndromic hearing loss 16, nonsyndromic genetic hearing loss (ClinVar).

How common is STRC p.Arg1073Ter (c.3217C>T) in the general population?

STRC p.Arg1073Ter (c.3217C>T) is very rare (popmax 0.00465%, sas) (gnomAD).

STRC p.Arg1073Ter

c.3217C>T · rs876657725 · VCV228402

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00465%, sas)

Conditions

Monogenic 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 13 of 29
Splicing
SpliceAI	Δ0.94	donor gain · deltas
Pangolin	Δ0.81	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.14	GERP -3.4
Overall
CADD	35.0	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 0.00465% South Asian · 3/64,576 alleles

Filtering AF 0.00123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000642%

Overall 0.000954% 8/838,452 alleles · very rare exomes 5/716,188 · genomes 3/122,264 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00465%	21,525
European (non-Finnish)	0.000937%	106,720

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.Arg1073Ter
Coding: c.3217C>T
MANE Select: NM_153700
dbSNP: rs876657725
Type: single nucleotide variant
Location: chr15:43611237 (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

Monogenic hearing loss

Also linked: autosomal recessive nonsyndromic hearing loss 16 nonsyndromic genetic hearing loss

Similar variants

STRC p.Arg1073Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
STRC c.4219-1G>A Pathogenic/Likely pathogenic ★★ same condition
STRC c.4701+1G>A Pathogenic/Likely 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-arg1073ter (accessed [today's date]).

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