Is CERT1 p.Ser611= (c.1833T>C) pathogenic?

CERT1 p.Ser611= (c.1833T>C) is classified Likely benign in CERT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-17). Ultra-rare (popmax 0.0535%, eas).

How common is CERT1 p.Ser611= (c.1833T>C) in the general population?

CERT1 p.Ser611= (c.1833T>C) is ultra-rare (popmax 0.0535%, eas) (gnomAD).

CERT1 p.Ser611=

c.1833T>C · rs373547173 · VCV746640

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0535%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -1.3, phastCons 1
Overall
CADD	9.037	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0535% East Asian · 24/44,856 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.00688% 111/1,613,914 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0544%	1,838
East Asiangrpmax	0.0535%	1,869
South Asian	0.045%	2,222
African / African-American	0.00533%	18,762
Admixed American	0.00167%	60,022
European (non-Finnish)	0.000593%	168,545

Remaining individuals 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.Ser611=
Coding: c.1833T>C
MANE Select: NM_001379029
dbSNP: rs373547173
Type: single nucleotide variant
Location: chr5:75379388 (GRCh38)
Gene constraint: LOEUF 0.656 · pLI 0.10 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.75 · 27 PDB
Residue 611: 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-ser611 (accessed [today's date]).

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