Is STRA6 p.Trp15Ter (c.45G>A) pathogenic?

STRA6 p.Trp15Ter (c.45G>A) is classified Likely pathogenic in STRA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-30). Ultra-rare (popmax 0.0166%, mid); Associated with microphthalmia, syndromic 9.

What condition is associated with STRA6 p.Trp15Ter (c.45G>A)?

STRA6 p.Trp15Ter (c.45G>A) is associated with microphthalmia, syndromic 9 (ClinVar).

How common is STRA6 p.Trp15Ter (c.45G>A) in the general population?

STRA6 p.Trp15Ter (c.45G>A) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

STRA6 p.Trp15Ter

c.45G>A · VCV3892576

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Conditions

microphthalmia, syndromic 9

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.35	GERP -0.8, phastCons 0.69
Overall
CADD	7.719	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 0.0166% Middle Eastern · 1/6,012 alleles

Filtering AF 0.000651% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000243%

Overall 0.000782% 12/1,535,486 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,012
Admixed American	0.00392%	25,487
Remaining individualsnot grpmax-eligible	0.00333%	29,996
African / African-American	0.00137%	73,026
European (non-Finnish)	0.000523%	191,147

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.Trp15Ter
Coding: c.45G>A
MANE Select: NM_025055 · reported on NM_001199040
Type: single nucleotide variant
Location: chr15:74209410 (GRCh38)

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

Disease context

microphthalmia, syndromic 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-trp15ter (accessed [today's date]).

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