Is STRA6 p.Glu613Asp (c.1839A>T) pathogenic?

STRA6 p.Glu613Asp (c.1839A>T) is classified Uncertain significance in STRA6 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-07-12). AlphaMissense: likely benign (0.2157); Very rare (popmax 0.000427%, nfe); Associated with Inborn genetic diseases.

What condition is associated with STRA6 p.Glu613Asp (c.1839A>T)?

STRA6 p.Glu613Asp (c.1839A>T) is associated with Inborn genetic diseases (ClinVar).

How common is STRA6 p.Glu613Asp (c.1839A>T) in the general population?

STRA6 p.Glu613Asp (c.1839A>T) is very rare (popmax 0.000427%, nfe) (gnomAD).

What do computational predictors say about STRA6 p.Glu613Asp (c.1839A>T)?

AlphaMissense predicts likely benign (score 0.2157) — an in-silico prediction, not a clinical call.

STRA6 p.Glu613Asp

c.1839A>T · rs201008326 · VCV3030948

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2157 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000427%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2157	likely benign
REVEL	0.477	indeterminate
SaProt	LLR -7.47	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.33	donor loss, 1 bp away · masked 0 · deltas
Pangolin	Δ0.34	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.3	GERP 1.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 22 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000427% European (non-Finnish) · 5/1,172,150 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000312% 5/1,604,250 alleles · very rare exomes 5/1,452,002 · genomes 0/152,248 · joint denominator

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.Glu613Asp
Coding: c.1839A>T
MANE Select: NM_022369
dbSNP: rs201008326
Type: single nucleotide variant
Location: chr15:74180783 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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STRA6 p.Asp560Asn Uncertain significance ★★ ⚠ same condition
STRA6 p.His281Arg Uncertain significance ★★ ⚠ same condition
STRA6 p.Lys571Asn Uncertain significance ★★ same condition
STRA6 p.Met624Thr Uncertain significance ★★ ⚠ same condition
STRA6 p.Pro554Leu 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-glu613asp (accessed [today's date]).

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