Is CERT1 p.Arg211Cys (c.631C>T) pathogenic?

CERT1 p.Arg211Cys (c.631C>T) is classified Uncertain significance in CERT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely benign (0.0941); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with CERT1 p.Arg211Cys (c.631C>T)?

CERT1 p.Arg211Cys (c.631C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CERT1 p.Arg211Cys (c.631C>T) in the general population?

CERT1 p.Arg211Cys (c.631C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CERT1 p.Arg211Cys (c.631C>T)?

AlphaMissense predicts likely benign (score 0.0941) — an in-silico prediction, not a clinical call.

CERT1 p.Arg211Cys

c.631C>T · VCV4226714

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0941 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0941	likely benign
REVEL	0.153	moderately benign-leaning
SaProt	LLR -7.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 94 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	32.0	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 0.0011% South Asian · 1/90,972 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000685% 10/1,460,364 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,972
European (non-Finnish)	0.000763%	130,989

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.Arg211Cys
Coding: c.631C>T
MANE Select: NM_001379029
Type: single nucleotide variant
Location: chr5:75419389 (GRCh38)
Gene constraint: LOEUF 0.656 · pLI 0.10 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.75 · 27 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CERT1 p.Ser135Phe Likely pathogenic ★★ same condition
CERT1 c.-195C>T Uncertain significance ★★ same condition
CERT1 p.Ala538Val Uncertain significance ★★ ⚠ same condition
CERT1 p.Cys185Phe Uncertain significance ★★ ⚠ same condition
CERT1 p.Gly452Asp Uncertain significance ★★ ⚠ same condition
CERT1 p.Met133Val Uncertain significance ★★ ⚠ same condition
CERT1 c.-140C>T Likely benign ★★ same condition
CERT1 p.Ile489Val Likely benign ★★ same condition

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-arg211cys (accessed [today's date]).

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