Is CERCAM p.Arg495Pro (c.1484G>C) pathogenic?

CERCAM p.Arg495Pro (c.1484G>C) is classified Uncertain significance in CERCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-17). AlphaMissense: likely pathogenic (0.693); Very rare (popmax 8.48e-05%, nfe).

How common is CERCAM p.Arg495Pro (c.1484G>C) in the general population?

CERCAM p.Arg495Pro (c.1484G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CERCAM p.Arg495Pro (c.1484G>C)?

AlphaMissense predicts likely pathogenic (score 0.693) — an in-silico prediction, not a clinical call.

CERCAM p.Arg495Pro

c.1484G>C · rs142520790 · VCV2326687

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.693 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.693	likely pathogenic
REVEL	0.579	indeterminate
SaProt	LLR -12.43	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 0.79, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 15 kb · p 0.68 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.48e-05% European (non-Finnish) · 1/1,179,930 alleles

Overall 6.85e-05% 1/1,459,306 alleles · very rare

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: CERCAM
Protein: p.Arg495Pro
Coding: c.1484G>C
MANE Select: NM_016174
dbSNP: rs142520790
Type: single nucleotide variant
Location: chr9:128434562 (GRCh38)
Gene constraint: LOEUF 1.159 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.17

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

Similar variants

CERCAM p.Arg495His Uncertain significance ★ ⚠ same residue
CERCAM p.Ala294Gly Uncertain significance ★ ⚠ same type
CERCAM p.Ala353Thr Uncertain significance ★ ⚠ same type
CERCAM p.Ala39Thr Uncertain significance ★ ⚠ same type
CERCAM p.Ala489Thr Uncertain significance ★ ⚠ same type
CERCAM p.Ala534Thr Uncertain significance ★ ⚠ same type
CERCAM p.Ala543Asp Uncertain significance ★ ⚠ same type
CERCAM p.Ala543Thr 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/cercam-p-arg495pro (accessed [today's date]).

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