Is STRC p.Arg1237Trp (c.3709C>T) pathogenic?

STRC p.Arg1237Trp (c.3709C>T) is classified Uncertain significance in STRC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-06). AlphaMissense: likely benign (0.1285); Ultra-rare (popmax 0.0112%, afr); Associated with Inborn genetic diseases.

What condition is associated with STRC p.Arg1237Trp (c.3709C>T)?

STRC p.Arg1237Trp (c.3709C>T) is associated with Inborn genetic diseases (ClinVar).

How common is STRC p.Arg1237Trp (c.3709C>T) in the general population?

STRC p.Arg1237Trp (c.3709C>T) is ultra-rare (popmax 0.0112%, afr) (gnomAD).

What do computational predictors say about STRC p.Arg1237Trp (c.3709C>T)?

AlphaMissense predicts likely benign (score 0.1285) — an in-silico prediction, not a clinical call.

STRC p.Arg1237Trp

c.3709C>T · rs141745804 · VCV3171602

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1285 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1285	likely benign
REVEL	0.497	indeterminate
SaProt	LLR -10.26	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.093	GERP -1.5, phastCons 0.002
Regional constraint	o/e 0.42	unconstrained · MANE · 2,460 bp · p 1.3e-10 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% African / African-American · 8/71,680 alleles

Filtering AF 0.00549% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00405%

Overall 0.00118% 19/1,609,130 alleles · ultra-rare exomes 12/1,460,566 · genomes 7/148,564 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0112%	8,960
Remaining individualsnot grpmax-eligible	0.00641%	15,590
European (non-Finnish)	0.000594%	168,474

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.Arg1237Trp
Coding: c.3709C>T
MANE Select: NM_153700
dbSNP: rs141745804
Type: single nucleotide variant
Location: chr15:43607948 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STRC p.Arg1237Gln Uncertain significance ★ ⚠ same residue
STRC c.4701+1G>A Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1102Gln Uncertain significance ★★ ⚠ same condition
STRC p.Arg1338Gln Uncertain significance ★★ ⚠ same condition
STRC p.Arg56His Uncertain significance ★★ ⚠ same condition
STRC p.Arg832Trp Uncertain significance ★★ same condition
STRC p.Arg92Gln Uncertain significance ★★ ⚠ same condition
STRC p.Cys1464Tyr Uncertain significance ★★ ⚠ 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-arg1237trp (accessed [today's date]).

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