Is CIMAP1D p.Arg19Trp (c.55C>T) pathogenic?

CIMAP1D p.Arg19Trp (c.55C>T) is classified Uncertain significance in CIMAP1D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.0917); Ultra-rare (popmax 0.0448%, afr).

How common is CIMAP1D p.Arg19Trp (c.55C>T) in the general population?

CIMAP1D p.Arg19Trp (c.55C>T) is ultra-rare (popmax 0.0448%, afr) (gnomAD).

What do computational predictors say about CIMAP1D p.Arg19Trp (c.55C>T)?

AlphaMissense predicts likely benign (score 0.0917) — an in-silico prediction, not a clinical call.

CIMAP1D p.Arg19Trp

c.55C>T · VCV4653875

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0917 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0448%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0917	likely benign
REVEL	0.451	indeterminate
SaProt	LLR -7.97	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -3.2, phastCons 0.99
Regional constraint	o/e 1.05	unconstrained · MANE · 11 kb · p 0.28 · regional, not allelic
Overall
CADD	19.84	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 0.0448% African / African-American · 33/73,658 alleles

Filtering AF 0.0327% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0286%

Overall 0.00325% 51/1,568,074 alleles · ultra-rare exomes 33/1,415,734 · genomes 18/152,340 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0448%	2,232
Admixed American	0.00183%	54,688
Remaining individualsnot grpmax-eligible	0.00165%	60,476
European (non-Finnish)	0.0013%	77,086
South Asian	0.00118%	84,602

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: CIMAP1D
Protein: p.Arg19Trp
Coding: c.55C>T
MANE Select: NM_182577
Type: single nucleotide variant
Location: chr19:474693 (GRCh38)
Structure: AlphaFold pLDDT 67.70

Full CIMAP1D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMAP1D p.Ala255Ser Uncertain significance ★ ⚠ same type
CIMAP1D p.Ala66Thr Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg101Cys Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg11Gln Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg11Trp Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg136His Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg138Trp Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg148Cys 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/cimap1d-p-arg19trp (accessed [today's date]).

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