Is ACTR5 p.Pro103Ser (c.307C>T) pathogenic?

ACTR5 p.Pro103Ser (c.307C>T) is classified Uncertain significance in ACTR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: ambiguous (0.4946); Absent from gnomAD v4.1.

How common is ACTR5 p.Pro103Ser (c.307C>T) in the general population?

ACTR5 p.Pro103Ser (c.307C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTR5 p.Pro103Ser (c.307C>T)?

AlphaMissense predicts ambiguous (score 0.4946) — an in-silico prediction, not a clinical call.

ACTR5 p.Pro103Ser

c.307C>T · VCV4637171

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4946 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4946	ambiguous
REVEL	0.496	indeterminate
SaProt	LLR -6.37	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.57 · regional, not allelic
Overall
CADD	24.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACTR5
Protein: p.Pro103Ser
Coding: c.307C>T
MANE Select: NM_024855
Type: single nucleotide variant
Location: chr20:38748785 (GRCh38)
Gene constraint: LOEUF 0.986 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.75 · 6 PDB

Full ACTR5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTR5 p.Ala11Thr Uncertain significance ★ ⚠ same type
ACTR5 p.Ala13Val Uncertain significance ★ ⚠ same type
ACTR5 p.Ala14Thr Uncertain significance ★ ⚠ same type
ACTR5 p.Ala235Thr Uncertain significance ★ ⚠ same type
ACTR5 p.Ala253Thr Uncertain significance ★ ⚠ same type
ACTR5 p.Ala371Val Uncertain significance ★ ⚠ same type
ACTR5 p.Ala541Gly Uncertain significance ★ ⚠ same type
ACTR5 p.Arg210His 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/actr5-p-pro103ser (accessed [today's date]).

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