Is STRA6 p.Ala480= (c.1440C>T) pathogenic?

STRA6 p.Ala480= (c.1440C>T) is classified Likely benign in STRA6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-12). Ultra-rare (popmax 0.0387%, afr); Associated with STRA6-related disorder.

What condition is associated with STRA6 p.Ala480= (c.1440C>T)?

STRA6 p.Ala480= (c.1440C>T) is associated with STRA6-related disorder (ClinVar).

How common is STRA6 p.Ala480= (c.1440C>T) in the general population?

STRA6 p.Ala480= (c.1440C>T) is ultra-rare (popmax 0.0387%, afr) (gnomAD).

STRA6 p.Ala480=

c.1440C>T · rs143350697 · VCV3050350

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0387%, afr)

Conditions

STRA6-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.6	GERP -1.4, phastCons 0.99
Overall
CADD	13.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0387% African / African-American · 29/74,940 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0239%

Overall 0.00316% 51/1,614,034 alleles · ultra-rare exomes 39/1,461,824 · genomes 12/152,210 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0387%	2,584
Finnishnot grpmax-eligible	0.00469%	21,337
Admixed American	0.00167%	60,008
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.00144%	69,413

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.Ala480=
Coding: c.1440C>T
MANE Select: NM_022369
dbSNP: rs143350697
Type: single nucleotide variant
Location: chr15:74182241 (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

STRA6-related disorder

Similar variants

STRA6 p.Arg408Gly Uncertain significance ★★ ⚠ same condition
STRA6 p.Thr321Pro Uncertain significance ★★ ⚠ same condition
STRA6 c.1520+1G>T Likely pathogenic ★ same condition
STRA6 p.Arg508Ter Likely pathogenic ★ same condition
STRA6 p.Arg634Cys Uncertain significance ★ ⚠ same condition
STRA6 c.267-4C>T Likely benign same condition
STRA6 p.Leu118= Likely benign same condition
STRA6 c.267-1G>T Pathogenic/Likely pathogenic ★★ same type

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-ala480 (accessed [today's date]).

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