Is CREM p.Arg211Gln (c.632G>A) pathogenic?

CREM p.Arg211Gln (c.632G>A) is classified Uncertain significance in CREM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). AlphaMissense: likely benign (0.1383); Very rare (popmax 0.0022%, sas).

How common is CREM p.Arg211Gln (c.632G>A) in the general population?

CREM p.Arg211Gln (c.632G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CREM p.Arg211Gln (c.632G>A)?

AlphaMissense predicts likely benign (score 0.1383) — an in-silico prediction, not a clinical call.

CREM p.Arg211Gln

c.632G>A · rs543519388 · VCV2510051

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1383 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1383	likely benign
REVEL	0.381	indeterminate
SaProt	LLR -4.96	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 69 kb · p 0.17 · regional, not allelic
Overall
CADD	28.8	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R256Q vs ClinVar R211Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,060 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00062% 10/1,613,816 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,530
Admixed American	0.00167%	60,018
European (non-Finnish)	0.000593%	168,568

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: CREM
Protein: p.Arg211Gln
Coding: c.632G>A
MANE Select: NM_183011
dbSNP: rs543519388
Type: single nucleotide variant
Location: chr10:35206928 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 61.54

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

Similar variants

CREM p.Arg244= Benign ★★ same type
CREM p.Lys104= Benign ★★ same type
CREM p.Ser226Leu Likely benign ★★ ⚠ same type
CREM c.*344A>G Uncertain significance ★ ⚠ same type
CREM c.*354A>G Uncertain significance ★ ⚠ same type
CREM c.*368C>A Uncertain significance ★ same type
CREM p.Ala168Val Uncertain significance ★ ⚠ same type
CREM p.Ala58Ser 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/crem-p-arg211gln (accessed [today's date]).

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