Is CIMAP1D p.Pro191Ala (c.571C>G) pathogenic?

CIMAP1D p.Pro191Ala (c.571C>G) is classified Uncertain significance in CIMAP1D (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-26). AlphaMissense: likely benign (0.0559); Rare (popmax 0.197%, eas).

How common is CIMAP1D p.Pro191Ala (c.571C>G) in the general population?

CIMAP1D p.Pro191Ala (c.571C>G) is rare (popmax 0.197%, eas) (gnomAD).

What do computational predictors say about CIMAP1D p.Pro191Ala (c.571C>G)?

AlphaMissense predicts likely benign (score 0.0559) — an in-silico prediction, not a clinical call.

CIMAP1D p.Pro191Ala

c.571C>G · rs551126295 · VCV3235368

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0559 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.197%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0559	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -5.96	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 3.1	GERP -3.2, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 11 kb · p 0.28 · regional, not allelic
Overall
CADD	3.99	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 0.197% East Asian · 47/23,870 alleles

Filtering AF 0.152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.136%

Overall 0.00976% 54/553,520 alleles · rare exomes 48/407,984 · genomes 6/145,536 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.197%	508
Remaining individualsnot grpmax-eligible	0.00899%	11,121
Ashkenazi Jewishnot grpmax-eligible	0.00746%	13,408
European (non-Finnish)	0.00126%	79,088

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.Pro191Ala
Coding: c.571C>G
MANE Select: NM_182577
dbSNP: rs551126295
Type: single nucleotide variant
Location: chr19:464143 (GRCh38)
Structure: AlphaFold pLDDT 67.70
Residue 191: the 'disordered' region

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

Similar variants

CIMAP1D p.Pro191Arg Uncertain significance ★ ⚠ same residue
CIMAP1D p.Pro191Ser Uncertain significance ★ ⚠ same residue
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

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-pro191ala (accessed [today's date]).

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