Is CIMAP1D p.Pro140Leu (c.419C>T) pathogenic?

CIMAP1D p.Pro140Leu (c.419C>T) is classified Uncertain significance in CIMAP1D (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). AlphaMissense: likely benign (0.1338); Ultra-rare (popmax 0.0196%, eas).

How common is CIMAP1D p.Pro140Leu (c.419C>T) in the general population?

CIMAP1D p.Pro140Leu (c.419C>T) is ultra-rare (popmax 0.0196%, eas) (gnomAD).

What do computational predictors say about CIMAP1D p.Pro140Leu (c.419C>T)?

AlphaMissense predicts likely benign (score 0.1338) — an in-silico prediction, not a clinical call.

CIMAP1D p.Pro140Leu

c.419C>T · rs771308809 · VCV3235365

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1338 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0196%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1338	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -9.23	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 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 11 kb · p 0.28 · regional, not allelic
Overall
CADD	24.7	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 0.0196% East Asian · 8/40,820 alleles

Filtering AF 0.00969% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00705%

Overall 0.00344% 53/1,541,898 alleles · ultra-rare exomes 43/1,389,816 · genomes 10/152,082 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0196%	5,103
Admixed American	0.0126%	7,946
Remaining individualsnot grpmax-eligible	0.00502%	19,909
European (non-Finnish)	0.00297%	33,663
African / African-American	0.00138%	72,512
South Asian	0.0012%	83,390

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.Pro140Leu
Coding: c.419C>T
MANE Select: NM_182577
dbSNP: rs771308809
Type: single nucleotide variant
Location: chr19:464295 (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-pro140leu (accessed [today's date]).

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