Is CDIP1 p.Asp74His (c.220G>C) pathogenic?

CDIP1 p.Asp74His (c.220G>C) is classified Uncertain significance in CDIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: ambiguous (0.4241); Ultra-rare (popmax 0.0223%, eas).

How common is CDIP1 p.Asp74His (c.220G>C) in the general population?

CDIP1 p.Asp74His (c.220G>C) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about CDIP1 p.Asp74His (c.220G>C)?

AlphaMissense predicts ambiguous (score 0.4241) — an in-silico prediction, not a clinical call.

CDIP1 p.Asp74His

c.220G>C · rs745652579 · VCV2485832

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4241 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Computational evidence

Protein change
AlphaMissense	0.4241	ambiguous
REVEL	0.325	indeterminate
SaProt	LLR -7.21	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 1,555 bp · p 0.37 · regional, not allelic
Overall
CADD	22.4	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 0.0223% East Asian · 10/44,884 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.000806% 13/1,613,628 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,488
Admixed American	0.00334%	29,982
European (non-Finnish)	8.48e-05%	1,179,824

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: CDIP1
Protein: p.Asp74His
Coding: c.220G>C
MANE Select: NM_013399
dbSNP: rs745652579
Type: single nucleotide variant
Location: chr16:4513717 (GRCh38)
Gene constraint: LOEUF 1.142 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.37

Full CDIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDIP1 p.Ala122Thr Uncertain significance ★ ⚠ same type
CDIP1 p.Ala136Ser Uncertain significance ★ ⚠ same type
CDIP1 p.Ala34Gly Uncertain significance ★ ⚠ same type
CDIP1 p.Arg30His Uncertain significance ★ ⚠ same type
CDIP1 p.Asp48Asn Uncertain significance ★ ⚠ same type
CDIP1 p.Gln37Leu Uncertain significance ★ ⚠ same type
CDIP1 p.Gly172Arg Uncertain significance ★ ⚠ same type
CDIP1 p.His89Pro 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/cdip1-p-asp74his (accessed [today's date]).

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