Is CTRL p.Glu151Gln (c.451G>C) pathogenic?

CTRL p.Glu151Gln (c.451G>C) is classified Benign in CTRL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-22). AlphaMissense: likely benign (0.1404); Low-frequency (popmax 1.13%, afr).

How common is CTRL p.Glu151Gln (c.451G>C) in the general population?

CTRL p.Glu151Gln (c.451G>C) is low-frequency (popmax 1.13%, afr) (gnomAD).

What do computational predictors say about CTRL p.Glu151Gln (c.451G>C)?

AlphaMissense predicts likely benign (score 0.1404) — an in-silico prediction, not a clinical call.

CTRL p.Glu151Gln

c.451G>C · rs139670985 · VCV788454

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1404 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.13%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1404	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -5.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.16
Regional constraint	o/e 0.95	unconstrained · MANE · 1,915 bp · p 0.39 · regional, not allelic
Overall
CADD	6.347	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.13% African / African-American · 847/75,038 alleles

Filtering AF 1.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.04%

Overall 0.0602% 972/1,614,140 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.13%	89
Admixed American	0.128%	779
Middle Eastern	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.0576%	1,736
South Asian	0.0022%	45,541
European (non-Finnish)	0.000508%	196,674

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: CTRL
Protein: p.Glu151Gln
Coding: c.451G>C
MANE Select: NM_001907
dbSNP: rs139670985
Type: single nucleotide variant
Location: chr16:67930456 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.26
Residue 151: the peptidase s1 domain

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

Similar variants

CTRL p.Gly230Ser Uncertain significance ★★ ⚠ same type
CTRL p.Val70= Benign ★★ same type
CTRL p.Ala131Thr Uncertain significance ★ ⚠ same type
CTRL p.Ala27Thr Uncertain significance ★ ⚠ same type
CTRL p.Arg136His Uncertain significance ★ ⚠ same type
CTRL p.Arg162His Uncertain significance ★ ⚠ same type
CTRL p.Arg188Trp Uncertain significance ★ ⚠ same type
CTRL p.Arg242Cys 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/ctrl-p-glu151gln (accessed [today's date]).

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