Is STRC p.Ala1664fs (c.4989_4990del) pathogenic?

STRC p.Ala1664fs (c.49894990del) is classified Pathogenic in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-12). Very rare (popmax 0.00134%, afr).

How common is STRC p.Ala1664fs (c.4989_4990del) in the general population?

STRC p.Ala1664fs (c.4989_4990del) is very rare (popmax 0.00134%, afr) (gnomAD).

STRC p.Ala1664fs

c.4989_4990del · VCV3342645

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 26 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,704 alleles

Overall 6.2e-05% 1/1,612,856 alleles · very rare exomes 0/1,461,204 · genomes 1/151,652 · 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.Ala1664fs
Coding: c.4989_4990del
MANE Select: NM_153700
Type: Deletion
Location: chr15:43600537 (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

Similar variants

STRC p.Cys1599fs Pathogenic ★★ same type
STRC p.Glu1504fs Pathogenic/Likely pathogenic ★★ same type
STRC p.Leu1417_Leu1418insTer Pathogenic/Likely pathogenic ★★ same type
STRC p.Pro154fs Pathogenic ★★ same type
STRC p.Val724fs Pathogenic ★★ same type
STRC c.(?_1 Pathogenic ★ same type
STRC c.(?_3499 Pathogenic ★ same type
STRC c.3499_4701+1del Pathogenic ★ same type

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-ala1664fs (accessed [today's date]).

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