Is CIMAP1D p.Pro86Ser (c.256C>T) pathogenic?

CIMAP1D p.Pro86Ser (c.256C>T) is classified Uncertain significance in CIMAP1D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: likely pathogenic (0.5809); Very rare (popmax 0.00051%, nfe).

How common is CIMAP1D p.Pro86Ser (c.256C>T) in the general population?

CIMAP1D p.Pro86Ser (c.256C>T) is very rare (popmax 0.00051%, nfe) (gnomAD).

What do computational predictors say about CIMAP1D p.Pro86Ser (c.256C>T)?

AlphaMissense predicts likely pathogenic (score 0.5809) — an in-silico prediction, not a clinical call.

CIMAP1D p.Pro86Ser

c.256C>T · VCV4653880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5809 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00051%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5809	likely pathogenic · top 8% in CIMAP1D
REVEL	0.724	pathogenic-leaning
SaProt	LLR -7.79	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
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 1.05	unconstrained · MANE · 11 kb · p 0.28 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00051% European (non-Finnish) · 6/1,176,946 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000374% 6/1,606,368 alleles · very rare exomes 5/1,454,302 · genomes 1/152,066 · joint denominator

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.Pro86Ser
Coding: c.256C>T
MANE Select: NM_182577
Type: single nucleotide variant
Location: chr19:467742 (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-pro86ser (accessed [today's date]).

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