Is STRA6 p.Arg397= (c.1191A>G) pathogenic?

STRA6 p.Arg397= (c.1191A>G) is classified Likely benign in STRA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). Very rare (popmax 0.00686%, nfe); Associated with microphthalmia, syndromic 9.

What condition is associated with STRA6 p.Arg397= (c.1191A>G)?

STRA6 p.Arg397= (c.1191A>G) is associated with microphthalmia, syndromic 9 (ClinVar).

How common is STRA6 p.Arg397= (c.1191A>G) in the general population?

STRA6 p.Arg397= (c.1191A>G) is very rare (popmax 0.00686%, nfe) (gnomAD).

STRA6 p.Arg397=

c.1191A>G · rs373116551 · VCV741837

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00686%, 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 0.33	GERP -2.2, phastCons 1
Overall
CADD	2.012	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00686% European (non-Finnish) · 81/1,180,036 alleles

Filtering AF 0.00563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00514% 83/1,613,590 alleles · very rare exomes 72/1,461,380 · genomes 11/152,210 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00686%	14,568
African / African-American	0.00267%	37,465

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.Arg397=
Coding: c.1191A>G
MANE Select: NM_022369
dbSNP: rs373116551
Type: single nucleotide variant
Location: chr15:74183965 (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 p.Arg397Gln Uncertain significance ★ ⚠ same residue
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

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-arg397 (accessed [today's date]).

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