Is C2CD4B p.His90Gln (c.270C>G) pathogenic?

C2CD4B p.His90Gln (c.270C>G) is classified Uncertain significance in C2CD4B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). AlphaMissense: likely pathogenic (0.8161); Very rare (popmax 0.0024%, amr).

How common is C2CD4B p.His90Gln (c.270C>G) in the general population?

C2CD4B p.His90Gln (c.270C>G) is very rare (popmax 0.0024%, amr) (gnomAD).

What do computational predictors say about C2CD4B p.His90Gln (c.270C>G)?

AlphaMissense predicts likely pathogenic (score 0.8161) — an in-silico prediction, not a clinical call.

C2CD4B p.His90Gln

c.270C>G · rs1214670342 · VCV2242707

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8161 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0024%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8161	likely pathogenic · top 2% in C2CD4B
REVEL	0.515	indeterminate
SaProt	LLR -7.15	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -1.4, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 1,091 bp · p 0.0058 · regional, not allelic
Overall
CADD	20.2	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 0.0024% Admixed American · 1/41,616 alleles

Overall 7.54e-05% 1/1,326,558 alleles · very rare

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: C2CD4B
Protein: p.His90Gln
Coding: c.270C>G
MANE Select: NM_001007595
dbSNP: rs1214670342
Type: single nucleotide variant
Location: chr15:62164715 (GRCh38)
Structure: AlphaFold pLDDT 60.81

Full C2CD4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C2CD4B p.Ala138Thr Uncertain significance ★ ⚠ same type
C2CD4B p.Ala190Gly Uncertain significance ★ ⚠ same type
C2CD4B p.Ala197Val Uncertain significance ★ ⚠ same type
C2CD4B p.Ala20Asp Uncertain significance ★ ⚠ same type
C2CD4B p.Ala231Pro Uncertain significance ★ ⚠ same type
C2CD4B p.Ala239Val Uncertain significance ★ ⚠ same type
C2CD4B p.Ala244Thr Uncertain significance ★ ⚠ same type
C2CD4B p.Ala244Val 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/c2cd4b-p-his90gln (accessed [today's date]).

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