Is STRA6 p.Arg508Ter (c.1522C>T) pathogenic?

STRA6 p.Arg508Ter (c.1522C>T) is classified Likely pathogenic in STRA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-19). Very rare (popmax 0.000509%, nfe); Associated with STRA6-related disorder.

What condition is associated with STRA6 p.Arg508Ter (c.1522C>T)?

STRA6 p.Arg508Ter (c.1522C>T) is associated with STRA6-related disorder (ClinVar).

How common is STRA6 p.Arg508Ter (c.1522C>T) in the general population?

STRA6 p.Arg508Ter (c.1522C>T) is very rare (popmax 0.000509%, nfe) (gnomAD).

STRA6 p.Arg508Ter

c.1522C>T · VCV4925822

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Conditions

STRA6-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -3.6, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,858 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,666 alleles · very rare exomes 6/1,461,432 · genomes 0/152,234 · 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: STRA6
Protein: p.Arg508Ter
Coding: c.1522C>T
MANE Select: NM_022369
Type: single nucleotide variant
Location: chr15:74181457 (GRCh38)
Gene constraint: LOEUF 0.725 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.18

Full STRA6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

STRA6-related disorder

Similar variants

STRA6 p.Arg408Gly Uncertain significance ★★ ⚠ same condition
STRA6 p.Thr321Pro Uncertain significance ★★ ⚠ same condition
STRA6 c.1520+1G>T Likely pathogenic ★ same condition
STRA6 p.Arg634Cys Uncertain significance ★ ⚠ same condition
STRA6 c.267-4C>T Likely benign same condition
STRA6 p.Ala480= Likely benign same condition
STRA6 p.Leu118= Likely benign same condition
STRA6 c.267-1G>T Pathogenic/Likely 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/stra6-p-arg508ter (accessed [today's date]).

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