Is CIMAP1C p.Pro253Ser (c.757C>T) pathogenic?

CIMAP1C p.Pro253Ser (c.757C>T) is classified Uncertain significance in CIMAP1C (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-27). AlphaMissense: likely benign (0.2518); Very rare (popmax 0.00988%, sas).

How common is CIMAP1C p.Pro253Ser (c.757C>T) in the general population?

CIMAP1C p.Pro253Ser (c.757C>T) is very rare (popmax 0.00988%, sas) (gnomAD).

What do computational predictors say about CIMAP1C p.Pro253Ser (c.757C>T)?

AlphaMissense predicts likely benign (score 0.2518) — an in-silico prediction, not a clinical call.

CIMAP1C p.Pro253Ser

c.757C>T · rs779827531 · VCV2207101

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2518 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2518	likely benign
REVEL	0.293	indeterminate
SaProt	LLR -9.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.47, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 3,337 bp · p 0.17 · regional, not allelic
Overall
CADD	21.0	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 0.00988% South Asian · 9/91,068 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.000682% 11/1,612,944 alleles · very rare exomes 11/1,460,572 · genomes 0/152,372 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00988%	10,119
European (non-Finnish)	0.00017%	589,605

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: CIMAP1C
Protein: p.Pro253Ser
Coding: c.757C>T
MANE Select: NM_175881
dbSNP: rs779827531
Type: single nucleotide variant
Location: chr15:75727472 (GRCh38)
Structure: AlphaFold pLDDT 69.94

Full CIMAP1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMAP1C p.Ala14Glu Uncertain significance ★ ⚠ same type
CIMAP1C p.Ala226Pro Uncertain significance ★ ⚠ same type
CIMAP1C p.Ala66Asp Uncertain significance ★ ⚠ same type
CIMAP1C p.Ala66Thr Uncertain significance ★ ⚠ same type
CIMAP1C p.Arg110His Uncertain significance ★ ⚠ same type
CIMAP1C p.Arg136His Uncertain significance ★ ⚠ same type
CIMAP1C p.Arg146Trp Uncertain significance ★ ⚠ same type
CIMAP1C p.Arg147His 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/cimap1c-p-pro253ser (accessed [today's date]).

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