Is STRA6 p.Arg73Ser (c.217C>A) pathogenic?

STRA6 p.Arg73Ser (c.217C>A) is classified Uncertain significance in STRA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2014-09-03). AlphaMissense: ambiguous (0.3637); Very rare (popmax 0.00137%, afr).

How common is STRA6 p.Arg73Ser (c.217C>A) in the general population?

STRA6 p.Arg73Ser (c.217C>A) is very rare (popmax 0.00137%, afr) (gnomAD).

What do computational predictors say about STRA6 p.Arg73Ser (c.217C>A)?

AlphaMissense predicts ambiguous (score 0.3637) — an in-silico prediction, not a clinical call.

STRA6 p.Arg73Ser

c.217C>A · rs200203042 · VCV197335

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3637 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3637	ambiguous
REVEL	0.704	pathogenic-leaning
SaProt	LLR -7.17	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -2.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 22 kb · p 0.0065 · regional, not allelic
Overall
CADD	18.99	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 0.00137% African / African-American · 1/73,130 alleles

Overall 6.45e-05% 1/1,550,506 alleles · very rare exomes 0/1,398,320 · genomes 1/152,186 · 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.Arg73Ser
Coding: c.217C>A
MANE Select: NM_022369
dbSNP: rs200203042
Type: single nucleotide variant
Location: chr15:74197387 (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

Similar variants

STRA6 c.267-1G>T Pathogenic/Likely pathogenic ★★ same type
STRA6 p.Arg532Ter Pathogenic ★★ same type
STRA6 p.Thr644Met Pathogenic ★★ ⚠ same type
STRA6 c.1840+4C>T Uncertain significance ★★ same type
STRA6 c.*10A>C Uncertain significance ★★ same type
STRA6 p.Ala54Ser Uncertain significance ★★ ⚠ same type
STRA6 p.Ala557Thr Uncertain significance ★★ ⚠ same type
STRA6 p.Ala557Val Uncertain significance ★★ ⚠ 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-arg73ser (accessed [today's date]).

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