Is C3AR1 p.Pro39Thr (c.115C>A) pathogenic?

C3AR1 p.Pro39Thr (c.115C>A) is classified Uncertain significance in C3AR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-04). AlphaMissense: likely benign (0.2493); Ultra-rare (popmax 0.0483%, sas).

How common is C3AR1 p.Pro39Thr (c.115C>A) in the general population?

C3AR1 p.Pro39Thr (c.115C>A) is ultra-rare (popmax 0.0483%, sas) (gnomAD).

What do computational predictors say about C3AR1 p.Pro39Thr (c.115C>A)?

AlphaMissense predicts likely benign (score 0.2493) — an in-silico prediction, not a clinical call.

C3AR1 p.Pro39Thr

c.115C>A · rs766597117 · VCV2367558

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2493 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0483%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2493	likely benign
REVEL	0.198	benign-leaning
SaProt	LLR -14.36	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.89, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 1,445 bp · p 0.85 · regional, not allelic
Overall
CADD	25.1	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 0.0483% South Asian · 44/91,084 alleles

Filtering AF 0.0369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.00378% 61/1,614,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0483%	2,070
Middle Eastern	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.008%	12,498
Admixed American	0.00167%	59,990
European (non-Finnish)	0.000763%	131,115

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: C3AR1
Protein: p.Pro39Thr
Coding: c.115C>A
MANE Select: NM_004054
dbSNP: rs766597117
Type: single nucleotide variant
Location: chr12:8060071 (GRCh38)
Gene constraint: LOEUF 1.58 · pLI 0.32 (gnomAD)
Structure: AlphaFold pLDDT 68.68 · 19 PDB
Residue 39: an α-helix

Full C3AR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C3AR1 p.Pro76Ala Uncertain significance ★★ ⚠ same type
C3AR1 p.Tyr90= Likely benign ★★ same type
C3AR1 p.Val136Ala Benign/Likely benign ★★ ⚠ same type
C3AR1 p.Val47Gly Benign ★★ ⚠ same type
C3AR1 c.-8G>A Uncertain significance ★ same type
C3AR1 p.Ala150Asp Uncertain significance ★ ⚠ same type
C3AR1 p.Ala288Asp Uncertain significance ★ ⚠ same type
C3AR1 p.Ala2Val 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/c3ar1-p-pro39thr (accessed [today's date]).

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