Is STRC p.Pro1718Ser (c.5152C>T) pathogenic?

STRC p.Pro1718Ser (c.5152C>T) is classified Uncertain significance in STRC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-08). AlphaMissense: likely benign (0.1009); Ultra-rare (popmax 0.0191%, nfe); Associated with Inborn genetic diseases.

What condition is associated with STRC p.Pro1718Ser (c.5152C>T)?

STRC p.Pro1718Ser (c.5152C>T) is associated with Inborn genetic diseases (ClinVar).

How common is STRC p.Pro1718Ser (c.5152C>T) in the general population?

STRC p.Pro1718Ser (c.5152C>T) is ultra-rare (popmax 0.0191%, nfe) (gnomAD).

What do computational predictors say about STRC p.Pro1718Ser (c.5152C>T)?

AlphaMissense predicts likely benign (score 0.1009) — an in-silico prediction, not a clinical call.

STRC p.Pro1718Ser

c.5152C>T · rs368600593 · VCV2360670

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1009 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0191%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1009	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -8.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1, phastCons 1
Regional constraint	o/e 0.18	constrained · MANE · 559 bp · p 2.3e-14 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0191% European (non-Finnish) · 225/1,179,452 alleles

Filtering AF 0.017% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0162%

Overall 0.0141% 228/1,612,354 alleles · ultra-rare exomes 217/1,461,446 · genomes 11/150,908 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0191%	5,242
Remaining individualsnot grpmax-eligible	0.0032%	31,217
African / African-American	0.00134%	74,398

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.Pro1718Ser
Coding: c.5152C>T
MANE Select: NM_153700
dbSNP: rs368600593
Type: single nucleotide variant
Location: chr15:43600047 (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 c.4701+1G>A Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1102Gln Uncertain significance ★★ ⚠ same condition
STRC p.Arg1237Trp 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-pro1718ser (accessed [today's date]).

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