Is STRA6 p.Asp122= (c.366C>T) pathogenic?

STRA6 p.Asp122= (c.366C>T) is classified Conflicting classifications of pathogenicity in STRA6 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-07-25). Ultra-rare (popmax 0.0495%, mid); Associated with microphthalmia, syndromic 9.

What condition is associated with STRA6 p.Asp122= (c.366C>T)?

STRA6 p.Asp122= (c.366C>T) is associated with microphthalmia, syndromic 9 (ClinVar).

How common is STRA6 p.Asp122= (c.366C>T) in the general population?

STRA6 p.Asp122= (c.366C>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

STRA6 p.Asp122=

c.366C>T · rs147428518 · VCV317116

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

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 1.6	GERP -3.7, phastCons 1
Overall
CADD	6.594	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,060 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0311%

Overall 0.0128% 207/1,614,016 alleles · ultra-rare exomes 193/1,461,790 · genomes 14/152,226 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,020
South Asian	0.0461%	2,168
Remaining individualsnot grpmax-eligible	0.0176%	5,681
European (non-Finnish)	0.0117%	8,551
Admixed American	0.0117%	8,575
East Asian	0.00669%	14,957
African / African-American	0.004%	25,003

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.Asp122=
Coding: c.366C>T
MANE Select: NM_022369
dbSNP: rs147428518
Type: single nucleotide variant
Location: chr15:74196048 (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 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
STRA6 p.Arg655Cys 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-asp122 (accessed [today's date]).

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