Is STRC p.Ala1593Val (c.4778C>T) pathogenic?

STRC p.Ala1593Val (c.4778C>T) is classified Pathogenic in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-09). AlphaMissense: ambiguous (0.5218); Very rare (popmax 0.00673%, eas); Associated with STRC-related disorder.

What condition is associated with STRC p.Ala1593Val (c.4778C>T)?

STRC p.Ala1593Val (c.4778C>T) is associated with STRC-related disorder (ClinVar).

How common is STRC p.Ala1593Val (c.4778C>T) in the general population?

STRC p.Ala1593Val (c.4778C>T) is very rare (popmax 0.00673%, eas) (gnomAD).

What do computational predictors say about STRC p.Ala1593Val (c.4778C>T)?

AlphaMissense predicts ambiguous (score 0.5218) — an in-silico prediction, not a clinical call.

STRC p.Ala1593Val

c.4778C>T · VCV4924491

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5218 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00673%, eas)

Conditions

STRC-related disorder

Computational evidence

Protein change
AlphaMissense	0.5218	ambiguous
REVEL	0.625	indeterminate
SaProt	LLR -10.18	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.6	GERP 2, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 511 bp · p 2.1e-05 · regional, not allelic
Overall
CADD	28.7	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 0.00673% East Asian · 3/44,576 alleles

Filtering AF 0.00335% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00348% 56/1,608,306 alleles · very rare exomes 50/1,459,804 · genomes 6/148,502 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00673%	14,859
European (non-Finnish)	0.00433%	23,099
Remaining individualsnot grpmax-eligible	0.00321%	31,128

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.Ala1593Val
Coding: c.4778C>T
MANE Select: NM_153700
Type: single nucleotide variant
Location: chr15:43600938 (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

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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-ala1593val (accessed [today's date]).

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