Is CTRL p.Gly230Ser (c.688G>A) pathogenic?

CTRL p.Gly230Ser (c.688G>A) is classified Uncertain significance in CTRL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-19). AlphaMissense: likely pathogenic (0.9008); Rare (popmax 0.131%, mid).

How common is CTRL p.Gly230Ser (c.688G>A) in the general population?

CTRL p.Gly230Ser (c.688G>A) is rare (popmax 0.131%, mid) (gnomAD).

What do computational predictors say about CTRL p.Gly230Ser (c.688G>A)?

AlphaMissense predicts likely pathogenic (score 0.9008) — an in-silico prediction, not a clinical call.

CTRL p.Gly230Ser

c.688G>A · rs774504385 · VCV2235216

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9008 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.131%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9008	likely pathogenic
REVEL	0.801	moderately pathogenic-leaning
SaProt	LLR -15.96	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	phastCons 0.98
Regional constraint	o/e 0.95	unconstrained · MANE · 1,915 bp · p 0.39 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.131% Middle Eastern · 8/6,084 alleles

Filtering AF 0.108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.0175% 283/1,614,008 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.131%	761
South Asian	0.127%	785
Ashkenazi Jewishnot grpmax-eligible	0.0338%	2,961
Remaining individualsnot grpmax-eligible	0.0256%	3,905
Admixed American	0.0183%	5,454
European (non-Finnish)	0.0102%	9,834
African / African-American	0.00267%	37,442

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.Gly230Ser
Coding: c.688G>A
MANE Select: NM_001907
dbSNP: rs774504385
Type: single nucleotide variant
Location: chr16:67930041 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.26
Residue 230: a disulfide bond; the peptidase s1 domain

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

Similar variants

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
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-gly230ser (accessed [today's date]).

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