Is ACTR5 p.Pro23Leu (c.68C>T) pathogenic?

ACTR5 p.Pro23Leu (c.68C>T) is classified Uncertain significance in ACTR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.0769); Absent from gnomAD v4.1.

How common is ACTR5 p.Pro23Leu (c.68C>T) in the general population?

ACTR5 p.Pro23Leu (c.68C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTR5 p.Pro23Leu (c.68C>T)?

AlphaMissense predicts likely benign (score 0.0769) — an in-silico prediction, not a clinical call.

ACTR5 p.Pro23Leu

c.68C>T · rs919739628 · VCV2354527

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0769 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,510,884)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0769	likely benign
REVEL	0.283	benign-leaning
SaProt	LLR -8.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.57 · regional, not allelic
Overall
CADD	23.1	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

No allele count reported in gnomAD v4.1 (AN 1,510,884). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACTR5
Protein: p.Pro23Leu
Coding: c.68C>T
MANE Select: NM_024855
dbSNP: rs919739628
Type: single nucleotide variant
Location: chr20:38748546 (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-pro23leu (accessed [today's date]).

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