Is STRC p.Arg1468Pro (c.4403G>C) pathogenic?

STRC p.Arg1468Pro (c.4403G>C) is classified Likely pathogenic in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). AlphaMissense: likely pathogenic (0.9534); Very rare (popmax 0.00017%, nfe); Associated with STRC-related disorder.

What condition is associated with STRC p.Arg1468Pro (c.4403G>C)?

STRC p.Arg1468Pro (c.4403G>C) is associated with STRC-related disorder (ClinVar).

How common is STRC p.Arg1468Pro (c.4403G>C) in the general population?

STRC p.Arg1468Pro (c.4403G>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about STRC p.Arg1468Pro (c.4403G>C)?

AlphaMissense predicts likely pathogenic (score 0.9534) — an in-silico prediction, not a clinical call.

STRC p.Arg1468Pro

c.4403G>C · VCV4924497

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9534 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

STRC-related disorder

Computational evidence

Protein change
AlphaMissense	0.9534	likely pathogenic ✓ concordant with ClinVar · top 3% in STRC
REVEL	0.644	pathogenic-leaning
SaProt	LLR -8.94	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 0.68, phastCons 0.99
Regional constraint	o/e 0.94	unconstrained · MANE · 3,913 bp · p 0.26 · regional, not allelic
Overall
CADD	25.6	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 0.00017% European (non-Finnish) · 2/1,179,886 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,694 alleles · very rare exomes 2/1,461,570 · genomes 0/152,124 · joint denominator

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.Arg1468Pro
Coding: c.4403G>C
MANE Select: NM_153700
Type: single nucleotide variant
Location: chr15:43603384 (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

STRC-related disorder

Similar variants

STRC p.Arg1468Ter Pathogenic ★★ same residue
STRC p.Arg1468Gln Uncertain significance ★ ⚠ same residue
STRC c.4219-1G>A Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1073Ter Pathogenic ★★ same condition
STRC p.Arg1338Ter Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1729Ter Pathogenic ★★ same condition
STRC p.Arg1730Ter Pathogenic/Likely pathogenic ★★ same condition
STRC p.Gln1343Ter Pathogenic/Likely 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-arg1468pro (accessed [today's date]).

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