Is CTRL p.Gly20Ser (c.58G>A) pathogenic?

CTRL p.Gly20Ser (c.58G>A) is classified Benign in CTRL (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-20). AlphaMissense: likely pathogenic (0.7908); Low-frequency (popmax 1.96%, afr).

How common is CTRL p.Gly20Ser (c.58G>A) in the general population?

CTRL p.Gly20Ser (c.58G>A) is low-frequency (popmax 1.96%, afr) (gnomAD).

What do computational predictors say about CTRL p.Gly20Ser (c.58G>A)?

AlphaMissense predicts likely pathogenic (score 0.7908) — an in-silico prediction, not a clinical call.

CTRL p.Gly20Ser

c.58G>A · rs140026167 · VCV707955

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7908 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.96%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7908	likely pathogenic
REVEL	0.266	benign-leaning
SaProt	LLR -12.58	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.23
Regional constraint	o/e 0.95	unconstrained · MANE · 1,915 bp · p 0.39 · regional, not allelic
Overall
CADD	16.24	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 1.96% African / African-American · 1,469/75,048 alleles

Filtering AF 1.87% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.84%

Overall 0.121% 1,949/1,613,998 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.96%	51
Admixed American	0.23%	435
Remaining individualsnot grpmax-eligible	0.184%	544
East Asian	0.131%	761
Middle Eastern	0.116%	866
European (non-Finnish)	0.013%	7,712
South Asian	0.00878%	11,386

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.Gly20Ser
Coding: c.58G>A
MANE Select: NM_001907
dbSNP: rs140026167
Type: single nucleotide variant
Location: chr16:67931196 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.26
Residue 20: a disulfide bond

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.Glu151Gln Benign ★★ 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

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-gly20ser (accessed [today's date]).

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