Is CTRL p.Gln48His (c.144G>C) pathogenic?

CTRL p.Gln48His (c.144G>C) is classified Conflicting classifications of pathogenicity in CTRL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-17). AlphaMissense: likely pathogenic (0.9366); Rare (popmax 0.779%, afr).

How common is CTRL p.Gln48His (c.144G>C) in the general population?

CTRL p.Gln48His (c.144G>C) is rare (popmax 0.779%, afr) (gnomAD).

What do computational predictors say about CTRL p.Gln48His (c.144G>C)?

AlphaMissense predicts likely pathogenic (score 0.9366) — an in-silico prediction, not a clinical call.

CTRL p.Gln48His

c.144G>C · rs79306830 · VCV785535

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9366 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.779%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9366	likely pathogenic
REVEL	0.348	indeterminate
SaProt	LLR -12.74	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.12	phastCons 0.94
Regional constraint	o/e 0.95	unconstrained · MANE · 1,915 bp · p 0.39 · regional, not allelic
Overall
CADD	22.6	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 0.779% African / African-American · 585/75,052 alleles

Filtering AF 0.727% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.706%

Overall 0.0373% 602/1,614,074 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.779%	128
Remaining individualsnot grpmax-eligible	0.0176%	5,683
Admixed American	0.00833%	12,005
South Asian	0.0011%	91,090

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.Gln48His
Coding: c.144G>C
MANE Select: NM_001907
dbSNP: rs79306830
Type: single nucleotide variant
Location: chr16:67931110 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.26
Residue 48: 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-gln48his (accessed [today's date]).

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