Is CERT1 p.Arg600= (c.1800A>G) pathogenic?

CERT1 p.Arg600= (c.1800A>G) is classified Benign/Likely benign in CERT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-14). Ultra-rare (popmax 0.0384%, nfe).

How common is CERT1 p.Arg600= (c.1800A>G) in the general population?

CERT1 p.Arg600= (c.1800A>G) is ultra-rare (popmax 0.0384%, nfe) (gnomAD).

CERT1 p.Arg600=

c.1800A>G · rs371046717 · VCV766008

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0384%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.531	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -0.2, phastCons 1
Overall
CADD	11.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0384% European (non-Finnish) · 453/1,179,824 alleles

Filtering AF 0.0354% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0343%

Overall 0.0408% 658/1,613,898 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.276%	362
European (non-Finnish)grpmax	0.0384%	2,604
Remaining individualsnot grpmax-eligible	0.032%	3,125
African / African-American	0.00666%	15,010
Admixed American	0.005%	20,004

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CERT1
Protein: p.Arg600=
Coding: c.1800A>G
MANE Select: NM_001379029
dbSNP: rs371046717
Type: single nucleotide variant
Location: chr5:75379421 (GRCh38)
Gene constraint: LOEUF 0.656 · pLI 0.10 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.75 · 27 PDB
Residue 600: the start domain; an α-helix

Full CERT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CERT1 p.Ser135Phe Likely pathogenic ★★ same type
CERT1 p.Thr166Ala Pathogenic/Likely pathogenic ★★ ⚠ same type
CERT1 c.-195C>T Uncertain significance ★★ same type
CERT1 p.Ala538Val Uncertain significance ★★ ⚠ same type
CERT1 p.Asp80Asn Uncertain significance ★★ ⚠ same type
CERT1 p.Cys185Phe Uncertain significance ★★ ⚠ same type
CERT1 p.Gly452Asp Uncertain significance ★★ ⚠ same type
CERT1 p.Lys48Asn 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/cert1-p-arg600 (accessed [today's date]).

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