Is STRC p.Phe1614= (c.4842C>T) pathogenic?

STRC p.Phe1614= (c.4842C>T) is classified Benign in STRC (ClinVar, Multiple submitters, 9 submitters; last evaluated 2024-11-27). Common (popmax 70.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive nonsyndromic hearing loss 16.

What condition is associated with STRC p.Phe1614= (c.4842C>T)?

STRC p.Phe1614= (c.4842C>T) is associated with autosomal recessive nonsyndromic hearing loss 16 (ClinVar).

STRC p.Phe1614=

Q: How common is STRC p.Phe1614= (c.4842C>T) in the general population?

STRC p.Phe1614= (c.4842C>T) is common (popmax 70.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4842C>T · rs3097773 · VCV177982

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 70.1%, afr) — 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/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.38	donor loss, 2 bp away · masked 0 · deltas
Pangolin	Δ0.38	loss · gain 0.15 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.28	GERP -1.6, phastCons 0.45
Overall
CADD	14.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 70.1% African / African-American · 52,060/74,232 alleles

Filtering AF 69.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 69.4%

Overall 14.9% 239,690/1,608,376 alleles · common exomes 196,190/1,457,324 · genomes 43,500/151,052 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	70.1%	1
East Asian	43%	2
Admixed American	21.5%	5
South Asian	19.6%	5
Ashkenazi Jewishnot grpmax-eligible	19.2%	5
Remaining individualsnot grpmax-eligible	17.5%	6
Middle Eastern	15.7%	6
Amishnot grpmax-eligible	10.7%	9
European (non-Finnish)	9.79%	10
Finnishnot grpmax-eligible	7.66%	13

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.Phe1614=
Coding: c.4842C>T
MANE Select: NM_153700
dbSNP: rs3097773
Type: single nucleotide variant
Location: chr15:43600874 (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-phe1614 (accessed [today's date]).

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