Is CDIPT p.Arg199His (c.596G>A) pathogenic?

CDIPT p.Arg199His (c.596G>A) is classified Uncertain significance in CDIPT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.1154); Ultra-rare (popmax 0.0162%, nfe).

How common is CDIPT p.Arg199His (c.596G>A) in the general population?

CDIPT p.Arg199His (c.596G>A) is ultra-rare (popmax 0.0162%, nfe) (gnomAD).

What do computational predictors say about CDIPT p.Arg199His (c.596G>A)?

AlphaMissense predicts likely benign (score 0.1154) — an in-silico prediction, not a clinical call.

CDIPT p.Arg199His

c.596G>A · rs780491326 · VCV2368362

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1154 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0162%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1154	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -8.19	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 4.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 3,665 bp · p 0.068 · regional, not allelic
Overall
CADD	22.3	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 0.0162% European (non-Finnish) · 190/1,172,068 alleles

Filtering AF 0.0143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.0127% 203/1,595,698 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0162%	6,169
Remaining individualsnot grpmax-eligible	0.0145%	6,874
African / African-American	0.00401%	24,909
Ashkenazi Jewishnot grpmax-eligible	0.00344%	29,066

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: CDIPT
Protein: p.Arg199His
Coding: c.596G>A
MANE Select: NM_006319
dbSNP: rs780491326
Type: single nucleotide variant
Location: chr16:29859235 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.02
Residue 199: a UniProt-annotated variant site (in)

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

Similar variants

CDIPT p.Ala140Ser Uncertain significance ★ ⚠ same type
CDIPT p.Ala146Ser Uncertain significance ★ ⚠ same type
CDIPT p.Ala206Val Uncertain significance ★ ⚠ same type
CDIPT p.Ala22Ser Uncertain significance ★ ⚠ same type
CDIPT p.Ala48Thr Uncertain significance ★ ⚠ same type
CDIPT p.Ala84Val Uncertain significance ★ ⚠ same type
CDIPT p.Arg115Gln Uncertain significance ★ ⚠ same type
CDIPT p.Arg138Lys 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/cdipt-p-arg199his (accessed [today's date]).

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