Is CDIN1 p.Arg259Gln (c.776G>A) pathogenic?

CDIN1 p.Arg259Gln (c.776G>A) is classified Uncertain significance in CDIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-24). AlphaMissense: likely benign (0.1661); Ultra-rare (popmax 0.0329%, mid).

How common is CDIN1 p.Arg259Gln (c.776G>A) in the general population?

CDIN1 p.Arg259Gln (c.776G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about CDIN1 p.Arg259Gln (c.776G>A)?

AlphaMissense predicts likely benign (score 0.1661) — an in-silico prediction, not a clinical call.

CDIN1 p.Arg259Gln

c.776G>A · rs753380905 · VCV2136760

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1661 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1661	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -6.75	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 229 kb · p 0.048 · regional, not allelic
Overall
CADD	26.2	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 0.0329% Middle Eastern · 2/6,080 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00285% 46/1,613,466 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,040
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,794
Remaining individualsnot grpmax-eligible	0.0048%	20,816
East Asian	0.00446%	22,440
African / African-American	0.00401%	24,962
European (non-Finnish)	0.00288%	34,695

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: CDIN1
Protein: p.Arg259Gln
Coding: c.776G>A
MANE Select: NM_001321759
dbSNP: rs753380905
Type: single nucleotide variant
Location: chr15:36808383 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.59

Full CDIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDIN1 p.Arg259Trp Uncertain significance ★ ⚠ same residue
CDIN1 p.Ala100Ser Uncertain significance ★★ ⚠ same type
CDIN1 p.Arg101Trp Uncertain significance ★★ ⚠ same type
CDIN1 p.Glu66Ala Uncertain significance ★★ ⚠ same type
CDIN1 p.Pro33Leu Uncertain significance ★★ ⚠ same type
CDIN1 p.Thr271Lys Uncertain significance ★★ ⚠ same type
CDIN1 p.Tyr236Cys Uncertain significance ★★ ⚠ same type
CDIN1 p.Val203Phe 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/cdin1-p-arg259gln (accessed [today's date]).

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