Is STRC p.Pro154fs (c.461del) pathogenic?

STRC p.Pro154fs (c.461del) is classified Pathogenic in STRC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-02-04). Very rare (popmax 0.00223%, eas); Associated with deafness-infertility syndrome.

What condition is associated with STRC p.Pro154fs (c.461del)?

STRC p.Pro154fs (c.461del) is associated with deafness-infertility syndrome (ClinVar).

How common is STRC p.Pro154fs (c.461del) in the general population?

STRC p.Pro154fs (c.461del) is very rare (popmax 0.00223%, eas) (gnomAD).

STRC p.Pro154fs

c.461del · rs1411667337 · VCV1120087

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

deafness-infertility syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.49	GERP -1.9
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,908 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000744% 12/1,613,954 alleles · very rare exomes 11/1,461,664 · genomes 1/152,290 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,908
Admixed American	0.00167%	60,010
Remaining individualsnot grpmax-eligible	0.0016%	62,472
Finnishnot grpmax-eligible	0.00156%	64,048
European (non-Finnish)	0.000678%	147,487

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.Pro154fs
Coding: c.461del
MANE Select: NM_153700
dbSNP: rs1411667337
Type: Deletion
Location: chr15:43617960 (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

deafness-infertility syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STRC c.4219-1G>A Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1224Ter Pathogenic ★★ same condition
STRC p.Arg1451Ter Pathogenic/Likely pathogenic ★★ same condition
STRC p.Gly1354Val Uncertain significance ★★ ⚠ same condition
STRC p.Pro1411Thr Uncertain significance ★★ ⚠ same condition
STRC p.Leu1639= Benign/Likely benign ★★ same condition
STRC p.Val1467Ile Likely benign ★★ same condition
STRC p.Arg1391Gly Conflicting classifications of pathogenicity ★ 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-pro154fs (accessed [today's date]).

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