Is STRA6 p.Val522= (c.1566G>T) pathogenic?

STRA6 p.Val522= (c.1566G>T) is classified Conflicting classifications of pathogenicity in STRA6 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2019-12-31). Ultra-rare (popmax 0.013%, nfe); Associated with microphthalmia, syndromic 9.

What condition is associated with STRA6 p.Val522= (c.1566G>T)?

STRA6 p.Val522= (c.1566G>T) is associated with microphthalmia, syndromic 9 (ClinVar).

How common is STRA6 p.Val522= (c.1566G>T) in the general population?

STRA6 p.Val522= (c.1566G>T) is ultra-rare (popmax 0.013%, nfe) (gnomAD).

STRA6 p.Val522=

c.1566G>T · rs886051474 · VCV317101

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.013%, nfe)

Conditions

microphthalmia, syndromic 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.7, phastCons 1
Overall
CADD	6.731	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.013% European (non-Finnish) · 153/1,179,752 alleles

Filtering AF 0.0113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0107%

Overall 0.0101% 163/1,613,398 alleles · ultra-rare exomes 149/1,461,408 · genomes 14/151,990 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.013%	7,711
Remaining individualsnot grpmax-eligible	0.0112%	8,923
African / African-American	0.00267%	37,414
Admixed American	0.00167%	59,950

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.Val522=
Coding: c.1566G>T
MANE Select: NM_022369
dbSNP: rs886051474
Type: single nucleotide variant
Location: chr15:74181413 (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

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

Similar variants

STRA6 p.Val522Gly Uncertain significance ★ ⚠ same residue
STRA6 c.267-1G>T Pathogenic/Likely pathogenic ★★ same condition
STRA6 p.Arg532Ter Pathogenic ★★ same condition
STRA6 p.Thr644Met Pathogenic ★★ ⚠ same condition
STRA6 c.*10A>C Uncertain significance ★★ same condition
STRA6 p.Ala54Ser Uncertain significance ★★ ⚠ same condition
STRA6 p.Ala557Val Uncertain significance ★★ ⚠ same condition
STRA6 p.Arg467Cys 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/stra6-p-val522 (accessed [today's date]).

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