Is STRA6 p.Ser345= (c.1035C>T) pathogenic?

STRA6 p.Ser345= (c.1035C>T) is classified Likely benign in STRA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-21). Very rare (popmax 0.00424%, nfe); Associated with microphthalmia, syndromic 9.

What condition is associated with STRA6 p.Ser345= (c.1035C>T)?

STRA6 p.Ser345= (c.1035C>T) is associated with microphthalmia, syndromic 9 (ClinVar).

How common is STRA6 p.Ser345= (c.1035C>T) in the general population?

STRA6 p.Ser345= (c.1035C>T) is very rare (popmax 0.00424%, nfe) (gnomAD).

STRA6 p.Ser345=

c.1035C>T · rs377002129 · VCV2085485

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00424%, 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 -9	GERP -3.9
Overall
CADD	0.401	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00424% European (non-Finnish) · 50/1,180,024 alleles

Filtering AF 0.00326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00294%

Overall 0.00353% 57/1,613,954 alleles · very rare exomes 54/1,461,786 · genomes 3/152,168 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00424%	23,600
African / African-American	0.00401%	24,967
Finnishnot grpmax-eligible	0.00312%	32,007
Remaining individualsnot grpmax-eligible	0.0016%	62,486
South Asian	0.0011%	91,042

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.Ser345=
Coding: c.1035C>T
MANE Select: NM_022369
dbSNP: rs377002129
Type: single nucleotide variant
Location: chr15:74189170 (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-ser345 (accessed [today's date]).

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