Is CIMAP1A p.Ser167Arg (c.501C>G) pathogenic?

CIMAP1A p.Ser167Arg (c.501C>G) is classified Uncertain significance in CIMAP1A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely pathogenic (0.5872); Ultra-rare (popmax 0.0179%, eas).

How common is CIMAP1A p.Ser167Arg (c.501C>G) in the general population?

CIMAP1A p.Ser167Arg (c.501C>G) is ultra-rare (popmax 0.0179%, eas) (gnomAD).

What do computational predictors say about CIMAP1A p.Ser167Arg (c.501C>G)?

AlphaMissense predicts likely pathogenic (score 0.5872) — an in-silico prediction, not a clinical call.

CIMAP1A p.Ser167Arg

c.501C>G · rs758873522 · VCV3235350

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5872 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5872	likely pathogenic
REVEL	0.101	moderately benign-leaning
SaProt	LLR -10.74	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,725 bp · p 0.21 · regional, not allelic
Overall
CADD	24.5	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 0.0179% East Asian · 8/44,776 alleles

Filtering AF 0.00885% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00642%

Overall 0.000496% 8/1,611,390 alleles · ultra-rare exomes 8/1,459,456 · genomes 0/151,934 · 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: CIMAP1A
Protein: p.Ser167Arg
Coding: c.501C>G
MANE Select: NM_053280
dbSNP: rs758873522
Type: single nucleotide variant
Location: chr11:198552 (GRCh38)
Structure: AlphaFold pLDDT 74.04

Full CIMAP1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMAP1A p.Ala156Thr Uncertain significance ★ ⚠ same type
CIMAP1A p.Ala203Asp Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg127Trp Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg14His Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg166His Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg186Cys Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg191Trp Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg205Pro 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/cimap1a-p-ser167arg (accessed [today's date]).

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