Is STRA6 p.Ala429Pro (c.1285G>C) pathogenic?

STRA6 p.Ala429Pro (c.1285G>C) is classified Likely pathogenic in STRA6 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.7405); Absent from gnomAD v4.1; Associated with microphthalmia, syndromic 9.

What condition is associated with STRA6 p.Ala429Pro (c.1285G>C)?

STRA6 p.Ala429Pro (c.1285G>C) is associated with microphthalmia, syndromic 9 (ClinVar).

How common is STRA6 p.Ala429Pro (c.1285G>C) in the general population?

STRA6 p.Ala429Pro (c.1285G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STRA6 p.Ala429Pro (c.1285G>C)?

AlphaMissense predicts likely pathogenic (score 0.7405) — an in-silico prediction, not a clinical call.

STRA6 p.Ala429Pro

c.1285G>C · rs2142004122 · VCV1064531

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7405 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microphthalmia, syndromic 9

Computational evidence

Protein change
AlphaMissense	0.7405	likely pathogenic ✓ concordant with ClinVar · top 4% in STRA6
REVEL	0.895	moderately pathogenic-leaning
SaProt	LLR -11.32	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 22 kb · p 0.0065 · regional, not allelic
Overall
CADD	26.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: STRA6
Protein: p.Ala429Pro
Coding: c.1285G>C
MANE Select: NM_022369
dbSNP: rs2142004122
Type: single nucleotide variant
Location: chr15:74183871 (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-ala429pro (accessed [today's date]).

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