Is STRC p.Glu1234= (c.3702G>A) pathogenic?

STRC p.Glu1234= (c.3702G>A) is classified Benign in STRC (ClinVar, Multiple submitters, 5 submitters; last evaluated 2021-07-15). Common (popmax 24.9%, mid) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive nonsyndromic hearing loss 16.

What condition is associated with STRC p.Glu1234= (c.3702G>A)?

STRC p.Glu1234= (c.3702G>A) is associated with autosomal recessive nonsyndromic hearing loss 16 (ClinVar).

STRC p.Glu1234=

Q: How common is STRC p.Glu1234= (c.3702G>A) in the general population?

STRC p.Glu1234= (c.3702G>A) is common (popmax 24.9%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3702G>A · rs62018890 · VCV165313

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 24.9%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

autosomal recessive nonsyndromic hearing loss 16

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.19	GERP -3.7, phastCons 0.34
Overall
CADD	5.196	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 24.9% Middle Eastern · 1,502/6,044 alleles

Filtering AF 23.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 23.4%

Overall 16.7% 268,882/1,608,708 alleles · common exomes 245,812/1,460,164 · genomes 23,070/148,544 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	24.9%	4
Ashkenazi Jewishnot grpmax-eligible	19.8%	5
South Asian	18%	6
European (non-Finnish)	17.8%	6
Remaining individualsnot grpmax-eligible	16.7%	6
African / African-American	15.6%	6
Amishnot grpmax-eligible	11.7%	9
Admixed American	11.1%	9
Finnishnot grpmax-eligible	10.9%	9
East Asian	0.134%	746

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.Glu1234=
Coding: c.3702G>A
MANE Select: NM_153700
dbSNP: rs62018890
Type: single nucleotide variant
Location: chr15:43607955 (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-glu1234 (accessed [today's date]).

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