Is STRC p.Pro88Leu (c.263C>T) pathogenic?

STRC p.Pro88Leu (c.263C>T) is classified Uncertain significance in STRC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-01). AlphaMissense: likely benign (0.1171); Very rare (popmax 0.00823%, amr); Associated with Inborn genetic diseases.

What condition is associated with STRC p.Pro88Leu (c.263C>T)?

STRC p.Pro88Leu (c.263C>T) is associated with Inborn genetic diseases (ClinVar).

How common is STRC p.Pro88Leu (c.263C>T) in the general population?

STRC p.Pro88Leu (c.263C>T) is very rare (popmax 0.00823%, amr) (gnomAD).

What do computational predictors say about STRC p.Pro88Leu (c.263C>T)?

AlphaMissense predicts likely benign (score 0.1171) — an in-silico prediction, not a clinical call.

STRC p.Pro88Leu

c.263C>T · VCV3963575

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1171 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00823%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1171	likely benign
REVEL	0.292	indeterminate
SaProt	LLR -6.70	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 0.71, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 7,566 bp · p 1.3e-74 · regional, not allelic
Overall
CADD	21.6	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 0.00823% Admixed American · 4/48,586 alleles

Filtering AF 0.00272% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00377% 38/1,007,932 alleles · very rare exomes 35/872,026 · genomes 3/135,906 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00823%	12,147
East Asian	0.00797%	12,555
South Asian	0.00559%	17,891
Remaining individualsnot grpmax-eligible	0.00471%	21,253
Ashkenazi Jewishnot grpmax-eligible	0.00399%	25,050
European (non-Finnish)	0.00355%	28,189

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.Pro88Leu
Coding: c.263C>T
MANE Select: NM_153700
Type: single nucleotide variant
Location: chr15:43618158 (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-pro88leu (accessed [today's date]).

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