Is STRA6 p.Pro85= (c.255C>T) pathogenic?

STRA6 p.Pro85= (c.255C>T) is classified Likely benign in STRA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). Ultra-rare (popmax 0.0107%, sas); Associated with microphthalmia, syndromic 9.

What condition is associated with STRA6 p.Pro85= (c.255C>T)?

STRA6 p.Pro85= (c.255C>T) is associated with microphthalmia, syndromic 9 (ClinVar).

How common is STRA6 p.Pro85= (c.255C>T) in the general population?

STRA6 p.Pro85= (c.255C>T) is ultra-rare (popmax 0.0107%, sas) (gnomAD).

STRA6 p.Pro85=

c.255C>T · VCV3709513

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, sas)

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 -3	GERP -4.4
Overall
CADD	1.732	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% South Asian · 9/84,032 alleles

Filtering AF 0.00553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00413%

Overall 0.00206% 32/1,549,914 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0107%	9,337
European (non-Finnish)	0.00192%	52,116
Remaining individualsnot grpmax-eligible	0.00166%	60,068

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.Pro85=
Coding: c.255C>T
MANE Select: NM_022369
Type: single nucleotide variant
Location: chr15:74197349 (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-pro85 (accessed [today's date]).

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