Is ARPC5L p.Pro37Ala (c.109C>G) pathogenic?

ARPC5L p.Pro37Ala (c.109C>G) is classified Uncertain significance in ARPC5L (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-24). AlphaMissense: likely benign (0.0454); Very rare (popmax 0.00151%, nfe).

How common is ARPC5L p.Pro37Ala (c.109C>G) in the general population?

ARPC5L p.Pro37Ala (c.109C>G) is very rare (popmax 0.00151%, nfe) (gnomAD).

What do computational predictors say about ARPC5L p.Pro37Ala (c.109C>G)?

AlphaMissense predicts likely benign (score 0.0454) — an in-silico prediction, not a clinical call.

ARPC5L p.Pro37Ala

c.109C>G · rs543171552 · VCV2551346

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0454 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00151%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0454	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -4.22	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 -0.34, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 7,646 bp · p 0.00034 · regional, not allelic
Overall
CADD	19.0	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 0.00151% European (non-Finnish) · 17/1,128,454 alleles

Filtering AF 0.000918% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00075%

Overall 0.00113% 17/1,508,826 alleles · very rare

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: ARPC5L
Protein: p.Pro37Ala
Coding: c.109C>G
MANE Select: NM_030978
dbSNP: rs543171552
Type: single nucleotide variant
Location: chr9:124869399 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI 0.87 (gnomAD)
Structure: AlphaFold pLDDT 89.33 · 3 PDB

Full ARPC5L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARPC5L p.Ala59Glu Uncertain significance ★ ⚠ same type
ARPC5L p.Ala72Thr Uncertain significance ★ ⚠ same type
ARPC5L p.Arg55Gln Uncertain significance ★ ⚠ same type
ARPC5L p.Arg55Gly Uncertain significance ★ ⚠ same type
ARPC5L p.Arg62Trp Uncertain significance ★ ⚠ same type
ARPC5L p.Glu29Ala Uncertain significance ★ ⚠ same type
ARPC5L p.Glu94Gln Uncertain significance ★ same type
ARPC5L p.Gly104Ser 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/arpc5l-p-pro37ala (accessed [today's date]).

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