Is STRC p.Pro1117Ser (c.3349C>T) pathogenic?

STRC p.Pro1117Ser (c.3349C>T) is classified Uncertain significance in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely benign (0.0651); Ultra-rare (popmax 0.0627%, afr); Associated with Inborn genetic diseases.

What condition is associated with STRC p.Pro1117Ser (c.3349C>T)?

STRC p.Pro1117Ser (c.3349C>T) is associated with Inborn genetic diseases (ClinVar).

How common is STRC p.Pro1117Ser (c.3349C>T) in the general population?

STRC p.Pro1117Ser (c.3349C>T) is ultra-rare (popmax 0.0627%, afr) (gnomAD).

What do computational predictors say about STRC p.Pro1117Ser (c.3349C>T)?

AlphaMissense predicts likely benign (score 0.0651) — an in-silico prediction, not a clinical call.

STRC p.Pro1117Ser

c.3349C>T · rs143103178 · VCV3171599

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0651 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0627%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0651	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -5.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.66	GERP -0.34, phastCons 0.45
Regional constraint	o/e 0.40	unconstrained · MANE · 226 bp · p 0.0011 · regional, not allelic
Overall
CADD	11.26	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 0.0627% African / African-American · 47/74,956 alleles

Filtering AF 0.0484% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0433%

Overall 0.00416% 67/1,611,632 alleles · ultra-rare exomes 37/1,460,056 · genomes 30/151,576 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0627%	1,595
Admixed American	0.00334%	29,917
South Asian	0.0022%	45,498
Remaining individualsnot grpmax-eligible	0.0016%	62,384
European (non-Finnish)	0.00127%	78,553

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.Pro1117Ser
Coding: c.3349C>T
MANE Select: NM_153700
dbSNP: rs143103178
Type: single nucleotide variant
Location: chr15:43610942 (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-pro1117ser (accessed [today's date]).

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