Is STRA6 p.Pro293Leu (c.878C>T) pathogenic?

STRA6 p.Pro293Leu (c.878C>T) is classified Conflicting classifications of pathogenicity in STRA6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-22). AlphaMissense: ambiguous (0.4887); Very rare (popmax 0.0011%, sas); Associated with microphthalmia, syndromic 9.

What condition is associated with STRA6 p.Pro293Leu (c.878C>T)?

STRA6 p.Pro293Leu (c.878C>T) is associated with microphthalmia, syndromic 9 (ClinVar).

How common is STRA6 p.Pro293Leu (c.878C>T) in the general population?

STRA6 p.Pro293Leu (c.878C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about STRA6 p.Pro293Leu (c.878C>T)?

AlphaMissense predicts ambiguous (score 0.4887) — an in-silico prediction, not a clinical call.

STRA6 p.Pro293Leu

c.878C>T · rs118203958 · VCV1133

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4887 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

microphthalmia, syndromic 9

Computational evidence

Protein change
AlphaMissense	0.4887	ambiguous
REVEL	0.774	moderately pathogenic-leaning
SaProt	LLR -11.88	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 22 kb · p 0.0065 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,074 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000558% 9/1,613,930 alleles · very rare exomes 7/1,461,826 · genomes 2/152,104 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,074
European (non-Finnish)	0.000678%	147,498

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.Pro293Leu
Coding: c.878C>T
MANE Select: NM_022369
dbSNP: rs118203958
Type: single nucleotide variant
Location: chr15:74190889 (GRCh38)
Gene constraint: LOEUF 0.725 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.18
Residue 293: the 'interaction with rbp1' region; a UniProt-annotated variant site (in mcops9)

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-pro293leu (accessed [today's date]).

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