Is STAR p.Arg272Pro (c.815G>C) pathogenic?

STAR p.Arg272Pro (c.815G>C) is classified Uncertain significance in STAR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-04). AlphaMissense: likely pathogenic (0.9825); Very rare (popmax 8.49e-05%, nfe).

How common is STAR p.Arg272Pro (c.815G>C) in the general population?

STAR p.Arg272Pro (c.815G>C) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about STAR p.Arg272Pro (c.815G>C)?

AlphaMissense predicts likely pathogenic (score 0.9825) — an in-silico prediction, not a clinical call.

STAR p.Arg272Pro

c.815G>C · VCV3629827

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9825 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9825	likely pathogenic · top 3% in STAR
REVEL	0.839	moderately pathogenic-leaning
SaProt	LLR -19.46	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 6,542 bp · p 0.84 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.49e-05% European (non-Finnish) · 1/1,178,292 alleles

Overall 6.21e-05% 1/1,609,836 alleles · very rare exomes 1/1,457,542 · genomes 0/152,294 · 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: STAR
Protein: p.Arg272Pro
Coding: c.815G>C
MANE Select: NM_000349
Type: single nucleotide variant
Location: chr8:38144316 (GRCh38)
Gene constraint: LOEUF 1.297 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.71 · 4 PDB
Residue 272: a UniProt-annotated variant site (in ah1; partial loss of activity); the start domain; an α-helix

Full STAR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

STAR p.Arg272Cys Pathogenic/Likely pathogenic ★★ same residue
STAR p.Arg272His Likely pathogenic ★★ same residue
STAR p.Arg272Ser Uncertain significance ★ ⚠ same residue
STAR p.Arg272Gly Uncertain significance ⚠ same residue
STAR p.Arg272fs Likely pathogenic ★ same residue
STAR c.178+1G>C Likely pathogenic ★★ same type
STAR c.306+1G>A Likely pathogenic ★★ same type
STAR c.307-1G>C 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/star-p-arg272pro (accessed [today's date]).

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