Is CCIN p.Arg327His (c.980G>A) pathogenic?

CCIN p.Arg327His (c.980G>A) is classified Uncertain significance in CCIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: likely benign (0.0836); Very rare (popmax 0.00801%, afr).

How common is CCIN p.Arg327His (c.980G>A) in the general population?

CCIN p.Arg327His (c.980G>A) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about CCIN p.Arg327His (c.980G>A)?

AlphaMissense predicts likely benign (score 0.0836) — an in-silico prediction, not a clinical call.

CCIN p.Arg327His

c.980G>A · VCV3997445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0836 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0836	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -9.30	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 8.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 1,763 bp · p 7.5e-07 · regional, not allelic
Overall
CADD	20.8	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 0.00801% African / African-American · 6/74,946 alleles

Filtering AF 0.00367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.00415% 67/1,613,968 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,491
Remaining individualsnot grpmax-eligible	0.0048%	20,828
European (non-Finnish)	0.00466%	21,455
East Asian	0.00223%	44,898
South Asian	0.0022%	45,548

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: CCIN
Protein: p.Arg327His
Coding: c.980G>A
MANE Select: NM_005893
Type: single nucleotide variant
Location: chr9:36170482 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 90.53

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

Similar variants

CCIN p.Arg485Trp Benign/Likely benign ★★ ⚠ same type
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CCIN p.Ala200Glu Uncertain significance ★ ⚠ same type
CCIN p.Ala200Thr Uncertain significance ★ ⚠ same type
CCIN p.Ala299Val Uncertain significance ★ ⚠ same type
CCIN p.Ala417Thr Uncertain significance ★ ⚠ same type
CCIN p.Ala536Ser Uncertain significance ★ ⚠ same type
CCIN p.Arg106Leu 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/ccin-p-arg327his (accessed [today's date]).

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