Is STRA6 p.Ser60= (c.180A>G) pathogenic?

STRA6 p.Ser60= (c.180A>G) is classified Uncertain significance in STRA6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-04). Rare (popmax 0.306%, eas); Associated with microphthalmia, syndromic 9.

What condition is associated with STRA6 p.Ser60= (c.180A>G)?

STRA6 p.Ser60= (c.180A>G) is associated with microphthalmia, syndromic 9 (ClinVar).

How common is STRA6 p.Ser60= (c.180A>G) in the general population?

STRA6 p.Ser60= (c.180A>G) is rare (popmax 0.306%, eas) (gnomAD).

STRA6 p.Ser60=

c.180A>G · rs186185335 · VCV884974

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.306%, eas)

Conditions

microphthalmia, syndromic 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.29	donor gain · deltas
Constraint at this position
Conservation	phyloP 0.29	GERP -1.5, phastCons 0.99
Overall
CADD	11.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.306% East Asian · 137/44,842 alleles

Filtering AF 0.264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.248%

Overall 0.0105% 170/1,613,330 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.306%	327
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,701
Remaining individualsnot grpmax-eligible	0.0112%	8,929
European (non-Finnish)	0.00153%	65,555

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.Ser60=
Coding: c.180A>G
MANE Select: NM_022369
dbSNP: rs186185335
Type: single nucleotide variant
Location: chr15:74197752 (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-ser60 (accessed [today's date]).

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