Is CTRL p.Val122Met (c.364G>A) pathogenic?

CTRL p.Val122Met (c.364G>A) is classified Uncertain significance in CTRL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). AlphaMissense: ambiguous (0.3886); Very rare (popmax 0.00415%, nfe).

How common is CTRL p.Val122Met (c.364G>A) in the general population?

CTRL p.Val122Met (c.364G>A) is very rare (popmax 0.00415%, nfe) (gnomAD).

What do computational predictors say about CTRL p.Val122Met (c.364G>A)?

AlphaMissense predicts ambiguous (score 0.3886) — an in-silico prediction, not a clinical call.

CTRL p.Val122Met

c.364G>A · rs1483618165 · VCV2550191

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00415%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3886	ambiguous
REVEL	0.309	indeterminate
SaProt	LLR -8.60	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7
Regional constraint	o/e 0.95	unconstrained · MANE · 1,915 bp · p 0.39 · regional, not allelic
Overall
CADD	14.83	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 0.00415% European (non-Finnish) · 49/1,180,036 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00342% 50/1,461,850 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00415%	24,082
African / African-American	0.00133%	75,038

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.Val122Met
Coding: c.364G>A
MANE Select: NM_001907
dbSNP: rs1483618165
Type: single nucleotide variant
Location: chr16:67930543 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.26
Residue 122: the peptidase s1 domain; 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-val122met (accessed [today's date]).

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