Is CDC45 p.Val81Ile (c.241G>A) pathogenic?

CDC45 p.Val81Ile (c.241G>A) is classified Benign/Likely benign in CDC45 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-03-01). AlphaMissense: likely benign (0.0681); Low-frequency (popmax 3.27%, mid).

How common is CDC45 p.Val81Ile (c.241G>A) in the general population?

CDC45 p.Val81Ile (c.241G>A) is low-frequency (popmax 3.27%, mid) (gnomAD).

What do computational predictors say about CDC45 p.Val81Ile (c.241G>A)?

AlphaMissense predicts likely benign (score 0.0681) — an in-silico prediction, not a clinical call.

CDC45 p.Val81Ile

c.241G>A · rs13447203 · VCV775656

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0681 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.27%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0681	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -6.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -0.43, phastCons 0.99
Regional constraint	o/e 0.90	unconstrained · MANE · 39 kb · p 0.0069 · regional, not allelic
Overall
CADD	12.02	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 3.27% Middle Eastern · 198/6,062 alleles

Filtering AF 2.89% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.75%

Overall 1.13% 18,195/1,612,744 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	3.27%	31
South Asian	2.11%	47
Finnishnot grpmax-eligible	1.33%	75
Remaining individualsnot grpmax-eligible	1.19%	84
European (non-Finnish)	1.18%	85
Admixed American	0.476%	210
Ashkenazi Jewishnot grpmax-eligible	0.456%	219
African / African-American	0.231%	434
East Asian	0.00446%	22,438

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: CDC45
Protein: p.Val81Ile
Coding: c.241G>A
MANE Select: NM_003504
dbSNP: rs13447203
Type: single nucleotide variant
Location: chr22:19482726 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.59 · 7 PDB
Residue 81: a UniProt-annotated variant site (in)

Full CDC45 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC45 p.Pro463Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
CDC45 c.653+4C>T Uncertain significance ★★ same type
CDC45 p.Ala373Val Uncertain significance ★★ ⚠ same type
CDC45 p.Ala38Asp Uncertain significance ★★ ⚠ same type
CDC45 p.Arg157His Uncertain significance ★★ ⚠ same type
CDC45 p.Arg175Gln Uncertain significance ★★ ⚠ same type
CDC45 p.Arg251His Uncertain significance ★★ ⚠ same type
CDC45 p.Arg269Trp 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/cdc45-p-val81ile (accessed [today's date]).

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