Is CAPS p.Arg71Gly (c.211C>G) pathogenic?

CAPS p.Arg71Gly (c.211C>G) is classified Uncertain significance in CAPS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-01). AlphaMissense: likely benign (0.1356); Very rare (popmax 0.00229%, nfe).

How common is CAPS p.Arg71Gly (c.211C>G) in the general population?

CAPS p.Arg71Gly (c.211C>G) is very rare (popmax 0.00229%, nfe) (gnomAD).

What do computational predictors say about CAPS p.Arg71Gly (c.211C>G)?

AlphaMissense predicts likely benign (score 0.1356) — an in-silico prediction, not a clinical call.

CAPS p.Arg71Gly

c.211C>G · rs550872985 · VCV2515121

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1356 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1356	likely benign
REVEL	0.195	benign-leaning
SaProt	LLR -9.53	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 1.4	GERP -2.4, phastCons 1
Overall
CADD	22.4	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R157G vs ClinVar R71G) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% European (non-Finnish) · 27/1,179,956 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00211% 34/1,613,756 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0094%	10,642
European (non-Finnish)grpmax	0.00229%	43,702
Remaining individualsnot grpmax-eligible	0.0016%	62,470

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CAPS
Protein: p.Arg71Gly
Coding: c.211C>G
MANE Select: NM_003716 · reported on NM_004058
dbSNP: rs550872985
Type: single nucleotide variant
Location: chr19:5914690 (GRCh38)
Structure: AlphaFold pLDDT 79.13 · 1 PDB
Residue 71: the 'disordered' region

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

Similar variants

CAPS p.Arg71Cys Uncertain significance ★ ⚠ same residue
CAPS p.Arg71His Uncertain significance ★ ⚠ same residue
CADPS p.Ser203= Benign ★★ same type
CADPS p.Tyr579= Benign ★★ same type
CAPS p.Arg18His Benign ★★ ⚠ same type
CAPS p.Pro88Thr Benign ★★ ⚠ same type
CADPS c.3477+2T>G Uncertain significance ★ same type
CADPS p.Ala1047Thr 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/caps-p-arg71gly (accessed [today's date]).

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