Is CIPC p.Arg310Gln (c.929G>A) pathogenic?

CIPC p.Arg310Gln (c.929G>A) is classified Uncertain significance in CIPC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.0626); Very rare (popmax 0.00267%, afr).

How common is CIPC p.Arg310Gln (c.929G>A) in the general population?

CIPC p.Arg310Gln (c.929G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CIPC p.Arg310Gln (c.929G>A)?

AlphaMissense predicts likely benign (score 0.0626) — an in-silico prediction, not a clinical call.

CIPC p.Arg310Gln

c.929G>A · VCV4229128

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0626 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0626	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -6.21	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	GERP -0.43, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 8,606 bp · p 0.0016 · regional, not allelic
Overall
CADD	21.2	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 0.00267% African / African-American · 2/74,912 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00142% 23/1,614,036 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,456
European (non-Finnish)	0.00169%	59,002
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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: CIPC
Protein: p.Arg310Gln
Coding: c.929G>A
MANE Select: NM_033426
Type: single nucleotide variant
Location: chr14:77114047 (GRCh38)
Gene constraint: LOEUF 0.64 · pLI 0.44 (gnomAD)
Structure: AlphaFold pLDDT 58.88

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

Similar variants

CIPC p.Arg310Trp Uncertain significance ★ ⚠ same residue
CIPC p.Ala220Thr Uncertain significance ★ ⚠ same type
CIPC p.Ala373Ser Uncertain significance ★ ⚠ same type
CIPC p.Arg29His Uncertain significance ★ ⚠ same type
CIPC p.Arg301Cys Uncertain significance ★ ⚠ same type
CIPC p.Arg301His Uncertain significance ★ ⚠ same type
CIPC p.Asn288His Uncertain significance ★ ⚠ same type
CIPC p.Asn319Ser 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/cipc-p-arg310gln (accessed [today's date]).

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