Is CCIN p.Arg185His (c.554G>A) pathogenic?

CCIN p.Arg185His (c.554G>A) is classified Uncertain significance in CCIN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). AlphaMissense: likely benign (0.1069); Ultra-rare (popmax 0.0802%, eas).

How common is CCIN p.Arg185His (c.554G>A) in the general population?

CCIN p.Arg185His (c.554G>A) is ultra-rare (popmax 0.0802%, eas) (gnomAD).

What do computational predictors say about CCIN p.Arg185His (c.554G>A)?

AlphaMissense predicts likely benign (score 0.1069) — an in-silico prediction, not a clinical call.

CCIN p.Arg185His

c.554G>A · rs142822017 · VCV3139678

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1069 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0802%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1069	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -5.68	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 6.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 1,763 bp · p 7.5e-07 · regional, not allelic
Overall
CADD	22.9	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 0.0802% East Asian · 36/44,896 alleles

Filtering AF 0.0594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0524%

Overall 0.00607% 98/1,614,016 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0802%	1,247
South Asian	0.0296%	3,374
Remaining individualsnot grpmax-eligible	0.0128%	7,810
Admixed American	0.0117%	8,572
African / African-American	0.00267%	37,464
Finnishnot grpmax-eligible	0.00156%	63,968
European (non-Finnish)	0.00144%	69,415

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.Arg185His
Coding: c.554G>A
MANE Select: NM_005893
dbSNP: rs142822017
Type: single nucleotide variant
Location: chr9:36170056 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 90.53
Residue 185: the back domain

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

Similar variants

CCIN p.Arg185Cys Uncertain significance ★ ⚠ same residue
CCIN p.Arg485Trp Benign/Likely benign ★★ ⚠ same type
CCIN p.Ala197Val Uncertain significance ★ ⚠ same type
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

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-arg185his (accessed [today's date]).

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